TATA-BINDING PROTEIN ASSOCIATED FACTORS, NUCLEIC ACIDS ENCODING TAFS, AND METHODS OF USE

Abstract: TATA-binding protein associated factors, TAFs, nuclear proteins involved in RNA polymerase I, II, and III transcription, and nucleic acids encoding TAFs are disclosed. The disclosed methods and compositions find use in developing pharmaceuticals, diagnosis and therapy.

Description: FOR THE PURPOSES OF INFORMATION ONLY Codes used to identify States party to the PCT on the front pages of pamphlets publishing international applications under the PCT. TATA-BINDING PROTEIN ASSOCIATED FACTORS, NUCLEIC ACIDS ENCODING TΛFS. AND METHODS OF USE The research carried out in the subject application was supported in part by grants from the National Institutes of Health. The government may have rights in any patent issuing on this application. CROSS-REFERENCE TO RELATED APPLICATION This Application is a continuation-in-part of Application Serial No. 08/087, 119 filed June 30, 1993, which is a continuation-in-part of Application Serial No. 08/013,412 filed January 28, 1993. INTRODUCTION Technical Field The technical field of this invention concerns TATA-binding protein associated factors, proteins involved in gene transcription. Background Gene transcription requires the concerted action of a number of molecules. DNA provides regulatory sequences and a coding sequence, or template, from which an RNA polymerase synthesizes corresponding RNA. Regulatory sequences generally include sites for sequence-specific transcriptional control, including promoters, enhancers, suppressors, etc; and also a site for transcription initiation. For review, see Mitchell and Tji.in ( 1989), Science 245, 371 -378. RNA polymerascs alone appear incapable of initiating transcription. However, in vitro transcriptional activity of RNA polymerases can be restored by the addition of nuclear extracts or fractions thereof. For example, under certain conditions, in vitro transcription by RNA polymerase II (Pol II) can be at least partially restored by the addition of what have variously been reported to be four, five, six or seven nuclear fractions [See e.g. Matsui et al. (1980), Biol Chem 255, 1192], herein referred to as TFIIΛ. TFIIB, TFI1D, TFIIE, TFIIF, TFIIH and TFIIJ. Pol I and Pol III appear to require at least two fractions, called respectively SL1 and UBF, and TFIIIA and TFIIIB. Many of these transcription fractions remain only partially characterized. For example, all but one ot ' the Pol II fractions remain incompletely characterized or comprise multiple components. The fractions TFIID, SL1 and TFIIB have been reported to contain a TΛTA binding component, henceforth, TATA-binding protein, or TBP. Groups of the present Applicants have reported anti-TBP antibodies capable of immunoprecipitating TBP from TFIID, SL1, and TFIIIB. TFIID, SL1 and TFIIIB immunoprecipitates have revealed TBP and numerous associated factors, tentatively called TBP-associated factors, or TAFs. Furthermore, preliminary experiments indicated that the TBP and non-TBP (TAF) fractions, when combined, facilitated at least some sequence-specific transcription activation. Unfortunately, it is not clear from the above art that there is any transcriptional activity in the non-TBP fractions of TFIID, SL1 or TFIIB immunoprecipitates. For example, the reported apparent functional complementarity of the TBP and non-TBP fractions might result from the influence of antirepressors, inhibitor inhibition, etc. Furthermore, the coactivator transcriptional activity attributed to the non-TBP fractions could result from one or more components unrelated to the electrophoretically resolved TAF components. Nor does the literature provide any suggestion as to which, if any, of the electrophoretically resolved components of the non-TBP fraction provide(s) transcriptional activity, nor means for identifying bands resolvable from the non- TBP fractions. Relevant Literature Pugh and Tjian ( 1990), Cell 61 : 1 187- 1 197; Tanese et al. (1991), Genes and Devel 5:2212-2224; Pugh and Tiian ( 1991). Genes and Devel 5: 1935-1945; Dynlacht et al. (1991 ), Cell 66:563-576; Timmers et al. ( 1991), Genes and Devel 5: 1946-1956; Zhou et al. ( 1992), Genes and Devel 6: 1964-1974; and Takada et al. (1992), Proc Nat I Acad Sci USA 89: 1 1809- 1 1813, relate to factors associated with Pol II transcription. Comai et al. ( 1992) Cell 68:965-976 relates to factors associated with Pol I transcription. Lobo et al. (1991), Genes and Devel, 5: 1477- 1489; Margotin et al. ( 1991 ), Science 251 :424-426; Simmen et al. (1991), EMBO J 10: 1853-1862; and Taggart et al. ( 1992), Cell 71 : 1015; Lobo et al. (1992), Cell 71: 1029; and White and Jackson ( 1992), Cell 71 : 1041 relate to factors associated with Pol III transcription. Sekiguchi et al. ( 1988), EMBO J 7: 1683-1687 and Sekiguchi et al. (1991 ), Mol and Cellular Biol 11:3317-3325 disclose the cloning of the CCG1 gene encoding a protein reported to be involved in cell cycle progression. SUMMARY OF THE INVENTION Substantially pure and biologically active TATA-binding protein associated factors (TAFs), eukaryotic nuclear proteins involved in RNA polymerase I, II, and III transcription, nucleic acids encoding TAFs, and methods of using TAFs and TAF-encoding nucleic acids are provided. Recombinant TAFs, anti-TAF antibodies and TΛF-fusion products find use in drug screening, diagnositcs and therapeutics. In particular, the disclosed TAFs provide valuable reagents in developing specific biochemical assays for screening compounds that agonize or antagonize selected transcription factors involved in regulating gene expression associated with human pathology. DESCRIPTION OF SPECIFIC EMBODIMENTS Substantially pure and biologically active TATA-binding protein associated factors (TAFs) and portions thereof, nucleic acids encoding TAFs and portions thereof, and methods of use are provided. As used herein, a given TΛF refers to the TAF protein, recombinant or purified from a natural source, and functional and xenogeneic analogs thereof. For 3 example "dTAFII l 10" refers to a Pol II TAF, deriveable from Drosophila, with an apparent molecular weight of about 1 10 kD. generally as determined by SDS- PAGE under conditions described herein, in Dynlacht et al. ( 1991), Comai et al. (1992), or otherwise identified by functional, sequence, etc. data herein. It is understood that these molecular weight designations are for the convenience of nomenclature and may not necessarily correspond to actual or predicted molecular weight. Other TAFs are analogously identified herein. A "portion" of a given TAF is a peptide comprising at least about a six, preferably at least about an eighteen, more preferably at least about a thirty-six amino acid sequence ot ' the TAF. Of particular interest are portions of the TAF that facilitate functional or structural interaction with activators, TAFs, TBP, Pol I, II or III, the TATA box and surrounding DNA sequences, etc. Methods for identifying such preferred portions are described below. By substantially full-length is meant a polypeptide or polynucleotide that comprises at least 50% , preferably at least 70% and more preferably at least 90% of the natural TAF polypeptide or polynucleotide length. "Xenogeneic" TAF analogs are nonhuman-, nonDrosophila-derived proteins with substantial functional or sequence identity to human and Drosophila TAFs. Of particular interest are xenogeneic TAF analogs derived from rodents, primates, and livestock animals including bovine, ovine, equine and avian species "Functional" analogs of a given TAF or proteins with "substantial functional identity" to a given TAF are compounds that exhibit one or more biochemical properties specific to such TAF, such as the ability of dTAFIIl 10 to interact with Sp 1. "Modulating transcription" means altering transcription, and includes changing the rate of transcription initiation, the level of transcription, or the responsiveness of transcription/transcription initiation to regulatory controls. The terms "substantially pure" or "isolated" mean that the TAF, TAF portion, or nucleic acid encoding a TAF or TAF portion is unaccompanied by at least some of the material with which it is normally associated in its natural state. While a composition of a substantially pure TAF or portion thereof is preferably substantially free of polyacrylamide. such composition may contain excipients and additives useful in diagnostic, therapeutic and investigative reagents. A 4 substantially pure TAF composition subject to electrophoresis or reverse phase HPLC provides such TAF as a single dtscernable protemaceous band or peak. Generally, a substantially pure TAF composition is at least about 1 % protein weight said TAT; preterablv at least about 10%; more preferably at least about 50%; and most preterablv at least 90% . Protein weight percentages are determined by dividing the weight ot the TAF or TAF portion, including alternative forms and analogs ot the TAF such as proteolytic breakdown products, alternatively spliced, differentially phosphorylated or glycosylated, or otherwise post-translationally modified lorms ot the TAF, present in a fraction by the total protein weight present A biologically active TA or TAF portion retains one or more of the TAF's native function such as the ability to specifically bind TBP, transcription factors (activators), other TAFs or anti-TAF antibodies, or to modulate or facilitate transcription or transcription initiation. Exemplary assays for biological activity are descπbed below and in the working exemplification. Specific binding is empirically determined by contacting, for example a TAF, with a mixture ot components and identifying those components that preferentially bind the TAF. Specific binding may be conveniently shown by competitive binding studies, lor example, immobilizing a TAF, on a solid matrix such as a polymer bead or microtiter plate and contacting the immobilized TAF with a mixture. 01 ten. one or more components of the mixture will be labelled. Another useful approach is to displace labelled ligand. Generally, specific binding of a TAF will have binding attmitv ot 10 M, preferably 10' M, more preferably 10' 10 M under optimized reaction conditions and temperature. Portions ol TAFs lind use in screening TAF expression libraries, defining functional domains of TAFs, identifying compounds that bind or associate with TAFs and the like. Accordingly, peptides encoding a portion of a TAF are provided that are capable ot modulating transcription including transcnption initiation. Typically, such peptides are effective by binding to a TAF, an activator, or TBP or competitively inhibiting a TAF domain's association with another compound. t\ pιcall\ a piotein like TBP or another TAF, an activator, or DNA. For example. FA I -TΛ1 interactions may be exploited to purify TAFs, e.g. immobilized TAF200 is used to purity TΛF1 10 Associational domains of TAFs are ascertainable by those skilled in the art using the methods and compositions disclosed herein. Useful methods include in vitro mutagenesis such as deletion mutants, secondary and tertiary structural predictions, antibody and solvent accessibility, etc. For example, peptides derived from highly charged regions find particular use as immunogens and as modulators of TAF-protein interactions. Also. TAF mutants are used to identify regions important for specific protein interactions or otherwise involved in transcription. Here, useful assays include column binding assay and transfection studies. The invention provides recombinantly produced TAFs, TAF analogs and portions thereof. These recombinant products are readily modified through physical, chemical, and olecular techniques disclosed or cited herein or otherwise known to those skilled in the relevant art. According to a particular embodiment of the invention, portions of the TΛF-encoding sequences are spliced with heterologous sequences to produce fusion proteins. Such fusion proteins find particular use in modulating gene transcription in vitro and in vivo. For example, many eukaryotic sequence-specific transcription factors have separable DNA binding and activation domains. A TAF or domain thereof can be fused to a well-characterized DNA binding domain (see, e.g., Sadowski et al., (1988) Nature 335, 563-564) and the resulting fusion protein can be tested for its ability to modulate transcription or transcriptional initiation. For example, we disclose the fusion of the N-terminal region of TAF110 to the DNA binding domain of the GAL4 protein. Alternatively, an TAF domain can be fused with a domain having endonuclease activity for site-specific DNA cleaving. Other useful TAF fusion partners include GST, Lerner epitope, an epitope recognized by a monoclonal antibody (e.g. hemagglutinin epitope and 12CA5 monoclonal antibody), glutathione S-transferase for immobilization, the SP1 or VP16 activation domains, etc. TAFs can be further modified by methods known in the art. For example, TAFs may be phosphorylated or dephosphorylated, glycosylated or deglycosylated, with or without radioactive labeling, etc. The disclosed TAF serine residues in particular provide useful phosphorylation sites. See e.g. methods disclosed in Roberts et al. ( 1991 ) Science 253. 1022-1026 and in Wegner et al. (1992) Science 256, 370-373. Especially useful are modifications that alter TAF solubility, membrane transportability, stability, and binding specificity and affinity. Some examples include fatty acid-acylation, proteolysis, and mutations in TAF-TAF or TAF-TBP interaction domains that stabilize binding. TAFs may also be modified with a label capable of providing a detectable signal, for example, at a heart muscle kinase labeling site, either directly or indirectly. Exemplary labels include radioisotopes, fluorescers, etc. Alternatively, a TAF may be expressed in the presence of a labelled amino acid such as 35 S- methionine. Such labeled TAFs and analogs thereof find use, for example, as probes in expression screening assays for proteins that interact with TAFs, or, for example, TAF binding to other transcription factors in drug screening assays. Specific polyclonal or monoclonal antibodies that can distinguish TAFs from other nuclear proteins are conveniently made using the methods and compositions disclosed in Harlow and Lane, Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, 1988, other references cited herein, as well as immunological and hybridoma technologies known to those in the art. In particular, TAFs and analogs and portions thereof also find use in raising anti-TAF antibodies in laboratory animals such as mice and rabbits as well as the production of monoclonal antibodies by cell fusion or transformation. Anti-TAF antibodies and fragments (Fab, etc) thereof find use in modulating TAF involvement in transcription complexes, screening TAF expression libraries, etc. in addition, these antibodies can be used to identify, isolate, and purify structural analogs of TAFs. Anti-TAF antibodies also find use for subcellular localization of TAFs under various conditions such as infection, during various cell cycle phases, induction with cytokines, protein kinases such as C and A, etc. Other exemplary applications include using TAF-specific antibodies (including monoclonal or TΛF-derived peptide specific antibodies) to immuno- deplete in vitro tran.scription extracts and using immuno-aff ity chromatography to purify TAFs, including analogs, or other nuclear factors which interact with TAFs. Compositions are also provided for therapeutic intervention in disease, for example, by modifying TAFs or TAF encoding nucleic acids. Oligopeptides can be synthesized in pure form and can find many uses in diagnosis and therapy. These oligopeptides can be used, for example, to modulate native TAF interaction with other TAFs, TBP. other transcription factors or DNA. The oligopeptides will generally be more than six and I ewer than about 60 amino acids, more usually fewer than about 30 ammo acids although large oligopeptides may be employed. A TAF or a portion thereol be used in purified form, generally greater than about 50%, usually greatei than about 90% pure Methods for purifying such peptides to such purities include various forms ot chromatographic, chemical, and electrophoretic separations disclosed herein or otherwise known to those skilled in the art. Experimental methods tor purifying TAFs are set out briefly below and in detail in the following working exemplification. Generally, TBP-TAF complexes are lmmunopuπtied (generally, bv lmmunoprecipitation) using polyclonal or monoclonal antibodies directed against a native TAF or TBP epitope. Alternatively, monoclonal antibodies directed against an epitope-tagged TBP or TAF may be used. See e.g Zhou, et al. ( 1992). At least three complementary experimental approaches are employed tor isolating cDNAs encoding TAFs: (1) TAF-specific binding proteins (e.g. antibodies directed against TAF proteins, TAF-bmding TAFs. TBP. . ΛF-bmdmg activators, or TAF-binding coactivators) are used for screening expression libraries; (2) cDNA libraries are screened with potentially homologous TAF oligonucleotide sequences (alternatively, a seπes of degenerate oligonucleotide PCR primers derived from the homologous TAF sequence may be used to amplily probes from cDNA. See Peterson et al. (1990) Science, 248, 1625-1630, I-igurel ), and, (3) TAF proteins are purified to homogeneity tor protein microsequencing TAF ENCODING NUCLEIC ACID The invention provides nucleic acid sequences encoding TAFs and portions of TAFs. By "encoding a portion ot a TAF" is meant to include sequences substantially identical to sequences encoding at least a portion of a TAF. Included are DNA and RNA sequences, sense and antisense. "Substantial sequence identity" means that a portion ot the protein or nucleic acid presents at least about 70%, more preferably at least about 80%, and most preferably at least about 90% sequence identity with a TAF sequence portion. Where the sequence diverges liom native TAF sequences disclosed herein, the differences are preferably consei ι e an acidic tor an acidic amino acid substitution or a nucleotide change providing a redundant codon. Dissimilar sequences are typically aggregated within regions rather than being distributed evenly over the polymer. A substantially identical sequence hybridizes to a complementary TAF- encoding sequence under low stringency conditions, for example, at 50°C and 6X SSC (0.9M saline/0.09M sodium citrate) and that remains bound when subject to washing at 55°C with I X SSC. The invention ' s TAF encoding polynucleotides are isolated; meaning that the claimed sequence is present as other than a naturally occurring chromosome or transcript in its natural environment. Typically isolated sequences are removed from at least some of the nucleotide sequences with which they are normally associated with on a natural chromosome. A substantially pure or isolated TAF- or TAF portion-encoding nucleic acid is generally at least about 1 % nucleic acid weight said TAF-encoding nucleic acid; preferably at least about 1 %: more preferably at least about 50%; and most preferably at least 90% . Nucleic acid weight percentages are determined by dividing the weight of the TAF or TAF portion-encoding nucleic acid, including alternative forms and analogs such as alternatively spliced or partially transcribed forms, by the total nucleic acid weight present. The invention also provides for TAF sequences modified by transitions, transversions, deletions, insertions, or other modifications such as alternative splicing and such alternative forms, genomic TAF sequences, TAF gene flanking sequences, including TAF regulatory sequences and other non-transcribed TAF sequences, TAF niRNΛ sequences, and RNA and DNA antisense sequences complementary to TAF encoding sequences, equences encoding xenogeneic TAFs. and TAF sequences comprising synthetic nucleotides, e.g., the oxygen of the phosphate group may be replaced with sulfur, methyl, or the like. For modified TAF-encoding sequences or related sequences encoding proteins with TΛF-like functions, there will generally be substantial sequence identity between at least a portion thereof and a portion of a TAF, preferably at least about 40%, more preferably at least 80%, most preferably at least 90%, particularly conservative substitutions, particularly within regulatory regions and regions encoding protein domains involved in protein-protein interactions, particularly TAF-transcripiion factor interactions. Typically, the invention ' s TAF encoding polynucleotides are associated with heterologous sequences, lij mpies of such heterologous sequences include regulatory sequences such as promoters, enhancers, response elements, signal sequences, polyadenylation sequences, etc. , introns, 5' and 3' noncoding regions, etc. Other useful heterologous sequences are known to those skilled in the art or otherwise disclosed references cited herein. See for example, Russel Doolittle, Of URFs and ORFs, A Primer on How to Analyze Derived Amino Acid Sequences, University Science Books, Mill Valley CA. TAF encoding nucleic acids can be subject to alternative purification, synthesis, modification or use by methods disclosed herein or otherwise known in the art. For example, the nucleic acids can be modified to alter stability, solubility, binding affinity and specificity, methylation, etc. The nucleic acid sequences of the present invention may also be modified with a label capable of providing a detectable signal, either directly or indirectly. Exemplary labels include radioisotopes, fiuorescers, biotinylation, etc. Nucleic acids encoding at least a portion of a TAF are used to identify nuclear factors which interact with that TAF using expression screening in yeast as described in Current Protocols in Molecular Biology. In this example, a yeast cDNA library containing fusion genes of cDNA joined with DNA encoding the activation domain of a transcription factor (e.g. Gal4) are transfected with fusion genes encoding a portion of a TAF and the DNA binding domain of a transcription factor. Clones encoding TAF binding proteins provide for the complementation of the transcription factor and are identified through transcription of a reporter gene. See, e.g. Fields and Song ( 1989) Nature 340, 245-246 and Chien et al. (1991) Proc Natl Acad Sci USA 88, 9578-9582. The invention also provides vectors comprising nucleic acids encoding a TAF or portion or analog thereof. A large number of vectors, including plasmid and viral vectors, have been described for expression in a variety of eukaryotic and prokaryotic hosts. Vectors will often include one or more replication systems for cloning or expression, one or more markers for selection in the host, e.g. antibiotic resistance, and one or more expression cassettes. The inserted TAF coding 10 sequences may be synthesized, isolated from natural sources, prepared as hybrids, etc. Ligation of the coding sequences to the transcriptional regulatory sequences may be achieved by known methods. Advantageously, vectors may also include a promotor operably linked to the TAF encoding portion. Suitable host cells may be transformed/transfected/infected by any suitable method including electroporation. CaCU mediated DNA uptake, viral infection, microinjection, micropr jectile. or other established methods. Alternatively, nucleic acids encoding one or more TAFs may be introduced into cells by recombination events. For example, a sequence can be microinjected into a cell, and thereby effect homologous recombination at the site of an endogenous gene encoding a TAF, an analog or pseudogene thereof, or a sequence with substantial identity to a TAF-encoding gene. Other recombination-based methods such as nonhomologous recombinations, deletion of endogenous gene by homologous recombination, especially in pluripotent cells, etc., provide additional applications. Appropriate host cells include bacteria, archebacteria, fungi, especially yeast, and plant and animal cells, especially mammalian cells. Of particular interest are E. coli. B. subtilis. Saccharomyces cerevisiae. SF9 and SF21 cells, C129 cells, 293 cells, Neurospora, and CHO, COS, HeLa cells and immortalized mammalian myeloid and lymphoid cell lines. Preferred replication systems include M13, ColEl, SV40. baculovirus, vaccinia, lambda, adenovirus, AAV, BPV, etc. A large number of tran.scription initiation and termination regulatory elements/ regions have been isolated and shown to be effective in the transcription and translation of heterologous proteins in the various hosts. Examples of these regions, methods of isolation, manner of manipulation, etc. are known in the art. The particular choice of vector/host cell is not critical to the invention. Under appropriate expression conditions, host cells are used as a source of recombinantly produced TAFs or TAF analogs. Preferred expression systems include E. Coli, vaccinia, or baculovirus; the latter two permitting the recombinant TAFs to be modified, processed and transported within a eukaryotic system. TAF-encoding oligonucleotides also used to identify other TAFs or transcription factors. For example. ''P-labeled TAF-encoding nucleic acids are used to screen cDNA libraries at low stringency to identify similar cDNAs that encode proteins with TΛI- ' -related domains. Additionally, TAF related proteins are 1 1 isolated by PCR amplification with degenerate oligonucleotide probes using the sequences disclosed herein. Other experimental methods for cloning TAFs, sequencing DNA encoding TΛ s. and expressing recombinant TAFs are also set out in the working exempli fication below. Other useful cloning, expression, and genetic manipulation techniques for practicing the inventions disclosed herein are known to those skilled in the art. The compositions and methods disclosed herein may be used to effect gene therapy. See, e.g. Gutierrez et al. ( 1992) Lancet 339, 715-721. For example, cells are transfected with TAF sequences operably linked to gene regulatory sequences capable of effecting altered TAF expression or regulation. To modulate TAF translation, cells may be transfected with TAF complementary antisense polynucleotides. Antisense modulation may employ TAF antisense sequences operably linked to gene regulatory sequences. Cells are transfected with a vector comprising a TAF sequence with a promoter sequence oriented such that transcription of the gene yields an antisense transcript capable of binding to TAF encoding mRNA. Transcription may be constitutive or inducible and the vector may provide for stable extrachromosomal maintenance or integration. Alternatively, single-stranded antisense nucleic acid sequences that bind to genomic DNA or mRNA encoding at least a portion of TAF may be administered to the target cell at a concentration that results in a substantial reduction in TAF expression. ASSAYS FOR IDENTIFYI NG TRANSCRIPTION FACTORS AND THERAPEUTIC AGENTS The invention provides methods and compositions for identifying agents useful in modulating gene transcription. Such agents find use in the diagnosis or treatment of broad range of disease including cancer, cardiovascular diseases, microbial and fungal infections and particularly viral infections, inflammatory disease, immune disease, etc. The ability to develop rapid and convenient high- throughput biochemical assays for screening compounds that interfere with the process of transcription in human cells opens a new avenue for drug development. An overview of this therapeuitic approach is presented in Peterson & Baichwal (1993), Trends in Biotechnology, in press. Typically, prospective agents are screened from large libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis ot sacchaπcle. pepnde. and nucleic acid based compounds, see, e.g. Lam et al., ( 1991 ) Nature 354, 82-86. Alternatively, libraries of natural compounds in the form ot bacterial, fungal, plant and animal extracts are available or readily predicable. Additionally, natural and synthetically produced libraries and compounds are readily modified through conventional chemical, physical, and biochemical means. Examples ot such modifications are disclosed herein. Useful agents are identified with a range of assays employing TAFs or TAF encoding nucleic acids. As examples, protein binding assays, nucleic acid binding assays and gel shift assays arc useful approaches. Exemplary assays include assaying labeled TBP binding to immobilized TAF, labeled TAF or TAF peptide binding immobilized TBP, etc. Many appropπate assays are amenable to scaled- up, high throughput usage suitable for volume drug screening. Such screening will typically require the screening ol at least about 10, preferably at least about 100, and more preferably at least about 1000 prospective agents per week. The particular assay used will be determined by the particular nature of the TAF interactions. For instance, a prospective agent may modify with the function of a TAF but not with transcription complex assembly. For example, a molecule that binds to a TAF but does not disrupt complex assembly is identified more readily through labelled binding assays than through gel retardation assay. Assays may employ single TAFS. TAF portions. TAF fusion products, partial TAF complexes, or the complete TFIID transcription complex, depending on the associational requirements of the sui ect transcription factor. Useful agents are typically those that bind to or modify the association of transcription associated tactors. especially TAFs. Preferred agents include those capable of modulating the expression of Pol II genes, particulary oncogenes (including viral oncogenes such as adenovirus EIA, human papilloma E7, and cellular oncogenes such as Rb, P53. E2F, myc, fos/jun (API), abl, etc.), genes transcribed during viral infection or activation, and sterol regulated genes. Preferered agents modify, preferably disrupt. TAF-TAF, TAF-activator, TAF- coactivator (coactivators include OCΛ-B. dTAFII l 10, etc.) or TAF-TBP binding. An especially preferred usef ul agent disrupts the association of a disclosed hTAF, 1 with an activator, particularly a viral-specific activator, particularly an HIV- specific activator such as tat. Useful agents are found within numerous chemical classes, though typically they are organic compounds; preferably small organic compounds. Small organic compounds have a molecular weight of more than 50 yet less than about 2,500, preferably less than about 750. more preferably, less than about 250. Exemplary classes include peptides, saccharides, steroids, and the like. Selected agents may be modified to enhance efficacy, stability, pharmaceutical compatibility, and the like. Structural identification of an agent may be used to identify, generate, or screen additional agents. For example, where peptide agents are identified, they may be modified in a variety of ways to enhance their stability, such as using an unnatural amino acid, such as a D-amino acid, particularly D-alanine. by lunctionalizing the amino or carboxyl terminus, e.g., for the amino group, acylation or alkylation, and for the carboxyl group, esterification or amidification. or the like. Other methods of stabilization may include encapsulation, for example, in liposomes, etc. Agents may be prepared in a variety of ways known to those skilled in the art. For example, peptides under about 60 amino acids can be readily synthesized today using conventional commercially available automatic synthesizers. Alternatively, peptide (and protein and nucleic acid agents) are readily produced by known recombinant technologies. For therapeutic uses, the compositions and selected agents disclosed herein may be administered by any convenient way that will depend upon the nature of the compound. For small molecular weight agents, oral administration is preferred and enteric coatings may be iiulicated where the compound is not expected to retain activity after exposure to the stomach environment. Generally the amount administered will be empirically determined, typically in the range of about 1 to 1000 ug/kg of recipient. Large proteins are preferably administered parenterally, conveniently in a physiologically acceptable carrier, e.g., phosphate buffered saline, saline, deionized water, or the like. Typically, such compositions are added to a retained physiological fluid such as blood or synovial fluid. Generally, the amount administered will be empirically determined, typically in the range of about 10 to 14 1000 μg/kg of the recipient. Other additives may be included, such as stabilizers, bactericides, etc. These additives will be present in conventional amounts. The following examples are offered by way of illustration and not by way of limitation. EXAMPLES Additional exemplary materials and methods for the purification, cloning and expression of TAFs are described below. Additional exemplary functional assays are described in detail. While exemplified primarily for dTAFIIl 10, the disclosed methods find ready application to other TAFs by those skilled in the art and familiar with the methods hereinor found in standard manuals such as Molecular Cloning, A Laboratory Manual (2nd Ed., Sambrook, Fritsch and Maniatis, Cold Spring Harbor), Current Protocols in Molecular Biology (Eds. Ausubel, Brent, Kingston. Moore, Seidman, Smith and Struhl, Greene Publ. Assoc, Wiley-Interscicnce. NY. NY, 1992) Immunopurified dTFIID complex is necessary and sufficient to mediate Spl activation in vitro. In order to determine if the TFIID complex is sufficient to substitute for a partially-purified TFIID fraction, we have purified the TBP-TAF complex extensively by using an affinity resin coupled to a specific monoclonal antibody directed against TBP. Transcriptionally active TFIID purified from Drosophila embryos was obtained by eluting the complex from the antibody affinity resin with a low concentration (0.5 M) of guanidine hydrochloride in the presence of a synthetic peptide corresponding to the epitope recognized by monoclonal 42A11. The antibody used for the immunopurification remained bound to the protein G- sepharose beads and was found in the pellet. The proteins were electrophoresed on an 8 % polyacrylamide-SDS gel and detected by silver staining. The resultant gels reveal seven major TAFs in the complex ranging in size from 30 to over 200 kD. After dialysis of the purified TFIID complex to remove the peptide and denaturant, in vitro transcription reactions were carried out in the presence of basal factors that were isolated from Drosophila embryo nuclear extracts (Dynlacht et al., 1991 ; Wampler et al.. 1^90). Without the TFIID fraction there is no detectable transcription Purified, recombinant dTBP is able to direct basal but not activated transcription. In contrast, immunopurified TFIID complex is able to mediate basal expression and Sp l activation Sp l -dependent activation with the TFIID fraction is shown m lanes 7 and 8. For the in vitro transcπption assay, 2 ul of the immunopurif ied TFIID complex was assayed. Transcπption was assayed by pπmer extension. The results demonstrate that the immunopurified TFIID complex containing TBP and at least 7 specific TAFs is necessary and sufficient for Spl- dependent activation of transcription in vitro. As expected, the impure TFIID fraction also mediates transcriptional activation by Spl , while the recombinant TBP protein is only able to direct basal, but not activated transcription. The immunopurified complex is also able to support activation by other transcπption factors such as NTF- 1. Cloning and expression ot Drosophila TAFl 10 cDNAs Puπfied TFIID complex was used to immunize a mouse, and monoclonal antibodies were generated against TAFl 10 (see Expeπmental Procedures below). The serum from the immunized mouse was also collected and polyclonal antibodies used to screen a λgt l 1 expression library constructed from Drosophila embryo cDNA (Zinn et al.. 1988) One clone was tentatively classified as a TAFl 10 cDNA because it produced protein that cross-reacted with independently isolated anti-TAF 110 monoclonal antibodies. This partial cDNA clone was subsequently used as a probe to isolate hill-length cDNAs from a λgtlO library (Poole et al.,1985). The longest clone obtained was 4.6 kb. This cDNA is polyadenylated at the 3' end and appears to be nearly full-length, based on the size of the mRNA, as determined by Northern blot analysis. The 4.6 kb cDNA clone contains a long open reading frame coding tor a protein of 921 amino acids (SEQUENCE ID NO: l), with a calculated molecular weight of 99.4 kD and an estimated pi of 10.1. Within the predicted ammo acid sequence, there are 3 peptides That correspond to am o acid sequences determined Irom lys C peptides generated from HPLC purified TAFl 10. I or miciosequencing. the TFIID complex was immunopurified from fractionated embrvo nuclear extract, and the TAFs were separated from TBP and the antibody by elution w ith I M guanidine-HCl. The purified TAFs were fracuonated on a C4 reverse phase HPLC column. Three adjacent fractions 16 containing TAF 1 10 as the major species were cleaved with the protease lys-C, and the resulting peptides were purified and sequenced. Three peptide sequences were found that match the predicted amino acid sequence of the TAFl 10 cDNA We have expressed TAF 1 10 protein in a variety of cell types. The protein was expressed from the cloned gene in a baculovirus expression system and detected by western blot using a TAFl 10 monoclonal antibody. The protein encoded by the TAF l 10 cDNA has the same apparent molecular weight as the endogenous protein in the TFIID fraction derived from Drosophila cells, and the protein produced from the cloned gene cross-reacts with monoclonal antibodies directed against the TAFl 10 protein isolated from embryos. These results taken together demonstrate that the 4.6 kb cDNA encodes the full-length TAF110 protein. TAFl 10 appears to be a single copy gene in Drosophila based on low- stringency Southern blot analysis. The TAFl 10 gene is located at 72D,4-5 on the left arm of the third chromosome. There are not any previously identified Drosophila genes assigned to this chromosomal location (Lindsley and Zimm, 1992). Hybridomas producing antibodies against TAFl 10 were selected by screening cell culture supematants for those containing antibodies that specifically recognize the 1 10 kd protein in a western blot. For westerns, approximately 50 ug of the TFIID fraction was immunoprecipitated with antibodies against dTBP or TAFl 10. The α-TΛFI 10 monoclonal antibody 33G8 was obtained from a hybridoma culture medium and purified by binding to protein G-sepharose. Proteins were eluted from the resin by boiling in sample buffer, electrophoresed on 8% polyacrylamide gel. and silver stained. Several of the a-TAFl lO monoclonals that were obtained by this method specifically immunoprecipitate the same set of proteins as a-dTBP antibodies. This demonstrates that at least part of TAFl 10 is accessible to our antibodies, and therefore exposed in the native TFIID complex and positioned for interaction with activators. Monoclonal antibodies specific for other Drosophila TAFs can also immunopurify the same TFIID complex as a-TBP and α-TAFHO antibodies. Thus, there appears to be one predominant TBP-containing complex in the TFIID fraction, as opposed to a heterogeneous set of complexes containing different sets 17 of TAFs bound to TBP. Our methods are also used to determine if there are rare, perhaps tissue-specific. TBP-containing complexes that might contain different collections of TAFs or if the activity of the TAFs could be modulated by post- translational modifications. For example, TAF200 does not stain as intensely as the other TAFs and TBP. and. on this basis, might not be present in all complexes. However, this protein seems to be an authentic member of the major TFIID complex since antibodies directed against TAF200 immunopurify a set of proteins that appear to be identical to complexes purified by antibodies directed against TBP or other TAFs. The preparations of the purified TFIID complex contain some polypeptides that are less abundant than the major TAF proteins. Based on western analyses with rv-TAF antibodies, these minor species appear to be proteolytic breakdown products of larger TAFs or substoichiometric TAFs. The TAFl 10 coding sequence contains several regions which are rich in glutamine residues or rich in serine and threonine residues, and the C-terminal third of the protein is highly charged. The C-terminal region of the molecule contains 32% acidic or basic residues. We searched the existing data bases for genes similar to the TAFl 10 gene, and found that it is not highly homologous to any previously identified genes. In particular, TAFl 10 did not show any similarity to any DNA binding domains. Interestingly, Spl received one of the highest scores in the NBRF protein sequence data base search for similarity to TAFl 10. The amino terminal third of TAFl 10 has an organization similar to the activation domains of Spl , consisting of glutamine-rich regions flanked by serine-threonine rich domains. The two proteins share 21 % amino acid identity and 35% similarity over 260 residues. This unexpected similarity to Spl prompted us to consider a possible functional relationship between Spl and TAFl 10. In particular, whether the amino-termina! region of TAF " 1 1 might contain interaction surfaces for activators such as Spl , especially since the A and B glutamine-rich domains are responsible for mediating Spl -Spl interactions as well as activation. Indeed, one of the unique properties of Spl activation domains is their capacity to mediate a phenomenon called superactivation. in which a truncated form of Spl lacking the zinc fingers but containing glutamine-rich domains A and B is able to interact directly with DNA-bound full length Sp l . This interaction increases the number of activation domains at the promoter and can greatly enhance expression of a gene regulated by Spl binding sites. This type of interaction also appears to be involved in synergistic activation mediated by distaliy and proximally bound Spl . ?dTAF110 can function as a target for the Spl activation domains To test for functional homology between the similar domains, we asked if the N-terminal region of TAFl 10 could function as a target for the Spl activation domains in a superactivation assay. The amino terminal 308 residues of TAF110 were fused to the DNA binding domain of the GAL4 protein, G4(l-147), and tested in a transient cotransfection assay in Drosophila Schneider cells. This hybrid construct, by itself, weakly activates (4 fold) a reporter gene which is dependent on GAL4 binding sites. This low level of activity is similar to the modest activation observed with constructs containing the Spl B domain fused to GAL4. When this TAF l 10 hybrid construct is cotransfected with DNA expressing the gin-rich A and B domains of Spl, (N539), a 60 fold increase in transcription is observed. This 15 fold superactivation is dependent on the TAFl 10 sequences since Spl(N539) is unable to stimulate transcription when cotransfected with G4(l- 147) alone. The interaction with Spl apparently requires an extended region of TAF110 since GAL4 fusion proteins bearing TAFl 10 residues 1-137, 138-308, or 87-308 are unable to mediate superactivation by Spl . These results indicate that the N-terminal 308 amino acids of TAFl 10 are sufficient for mediating an interaction with the glutamine-rich activation domains of Spl that lead to superactivation. In the positive control for this experiment, a GAL4-SplB domain fusion is superactivated approximately 50 fold by the fingerless Spl mutant. In a search for other potential targets of Spl, we have tested some additional members of the TFIID complex for the ability to mediate superactivation by Spl . For example. GAL4 hybrids containing TAF40, TAF80, or the amino-terminal region ot ' dTBP were found to be inactive in the superactivation assay. This results shows that the interaction between TAFl 10 and Spl in Drosophila cells is quite specific and that other subunits of the TBP-TAF complex that we tested are unable to interact with the glutamine-rich activation domains of S l . dTAFHO and Spl interact in yeast The superactivation assay in Drosophila Schneider cells provided the first hint that TAFl 10 mav serve as a eoactivator tor Sp l However, it is difficult to assess in this assay whether I ' AF l 10 can interact with Spl in the absence of the other TAFs which are present in Drosophila cells. The superactivation assay also imposes certain limitations to the number and types of constructs that can be tested. Moreover, it seemed prudent to establish several independent assays to investigate the relationship between TAF l 10 and transcription activation domains. Therefore, we earned out two additional types of assays, one in vivo and one in vitro, to test the results obtained in Schneider cells First, we tested the ability of TAFl 10 and Spl to interact in a \ ersatιie assay lor protein-protein interaction which is earned out in yeast cells (Fields and Song. 1989). This strategy takes advantage of the modular organization ol eukaryotic transcription factors. In this assay, one of the partners to be tested is I used to the DNA binding domain of GAL4 and, in a separate molecule, the other partner is I used to the acidic activation domain (AAD). A functional activation domain is recruited to the target promoter beaπng GAL4 binding sites and the lacZ reporter gene is expressed only if there is a protein-protein interaction between the partners being tested. Full-length TAF l 10 as well as a variety of deletion mutants were fused to the DNA binding domain of GΛE4, G4( 1 - 147). In contrast to the situation in Drosophila cells, the ammo terminal region of TAFl 10 cannot activate transcription by itselt in yeast This result was anticipated since glutamme-πch activation domains have not been observed to function in yeast. As potential partners for TAF l 10, the Sp l activation domains were fused to the acidic activation domain ol GΛE4. Each ol the Sp l glutamine-rich activation domains A or B can independently interact with tull-length TAFl 10 as judged by activation of the reporter gene. In these experiments, yeast beaπng an integrated GALl:lacZ fusion were transformed w ith two plasmids: ( 1 ) fusions to the DNA binding domain of GAL4 (residues 1 - 147), and (2) fusions to the acidic activation domain (AAD; residues 768-8X 1 ol GΛL4), and the resulting 3-gal activity was measured (expressed in units/ mg ot protein). Interestingly, domain A of Spl appears to interact more el icientlv than domain B, and this correlates well with the previous finding that A is a better activator tor transcription than domain B (Courey and 20 Tjian, 1988). As in Drosophila cells, residues 1-308 of TAFl 10 are sufficient for the interaction, while regions 1- 137 and 138-308 are inactive. The full-length TAFl 10 fusion is more active than the N308 construct in this assay. Although this effect may be due to dil lerential protein expression, it is possible that the C- terminal regions ol TAF l 10 contribute to interactions with Spl . The protein- protein interaction assay in yeast further supports the idea that TAFl 10 interacts, directly or indirectly, with the activation domains of Spl , and the strength of this interaction appears to be correlated with transcriptional function. The other TAF proteins that have been tested in the superactivation assay or the yeast assay displayed no delectable interaction with Spl . However, the GAL4 fusion proteins that these assays rely on might not be able to participate in all the correct interactions because some surfaces could be sterically blocked. Therefore, additional strategies, such as the use of full length Spl, are used to test for other potential interactions. dTAFHO does not interact with other activators tested To determine whether the interaction between Spl and TAFl 10 is specific, or whether other types of activators also interact with TAFl 10, we used the yeast assay to test a variety of other activation domains including the acidic activation domain of GAL4 (Ma and Ptashne, 1987) and the proline-rich activation domain of CTF (Mermod et al. 1989). Neither of these two activators displayed any interaction with TAFl 10 m the yeast assay. In addition we tested activation domains from the Drosophila proteins Antennapedia (Antp) and bicoid (bed), both of which are glutamine-rich. Surprisingly, both of these glutamine-rich domains failed to interact with TAF l 10 in the yeast assay. Since TAFl 10 can interact with both Spl domains A and B. which have no significant homology other than high glutamine content, but not Antp and bed which are even more glutamine-rich than Spl, it appears that glutamine content alone may not be a sufficient criterion for the classification of functionally similar activation domains. In this regard, it may be useful to draw a distinction between the Spl activation domains, which are approximately 25% glutamine and flanked by seπne/threonine rich sequences, and the bed and Antp sequences, which are partially composed of uninterrupted stretches of glutamines and lack adjacent seπne/threonine sequences. 21 The N-terminal region ot TAFl 10, containing the glutamine-and seπne/threonine-πch sequences, is able to function as a weak activation domain in Drosophila cells, suggesting that this region can interact with a component of the native TFIID complex To determine whether the N-terminal region of TAFl 10 is similar to the Sp l actu ation domains which can mediate muitimeπzation, we tested for TAF110-TAF1 10 interactions We found that the N-terminal region of TAFl 10 is able to interact with itsell as judged bv activation of the lacZ reporter gene in the yeast assay (figure 6Λ) This is another example of functional similanty between the Sp l activation domains and the N-terminal region of TAFl 10, which can interact with each other as well themselves TBP and other TAFs tested do not interact with Sp l in yeast Since Sp l synergistically activates transcription through multiple sites even though it does not bind cooperatively to DNA, we sought to determine whether Spl works via interactions ith multiple targets or coactivators. We therefore tested two other members ot the TFIID complex, TAF40 and TAF80. Similar to the superactivation assay in Drosophila cells, neither TAF40 or TAF80 displayed any ability to interact ith Sp l under the conditions of the yeast assay. In addition, the conserved C-termmal domain of TBP was tested for Spl interaction in yeast but no interaction was observed. We were unable to test full-length dTBP in this assay because it f unctions as an activator in yeast when fused to the GAL4 DNA binding domain These icsults show that the interaction between TAFl 10 and Spl is quite speci l ic. and that FAF80, TAF40, and the conserved region of TBP do not appear to be tai ets tor Sp l Since the TFIID complex is also required at promoters that lack a TATA box, one ot the TΛ1 s might be required tor promoter recognition through the initiator element. In addition to communicating with promoter-selective factors, the TAFs interact with each other, at least one TAF interacts with TBP, and one interacts with RNA polymei ase l i or one ot the basal factors. Spl binds dTΛF l 10 in \ ιtι o The superactiv ation assay m Schneider cells and the yeast experiments are both indirect assays lot piotem-prote interactions. Therefore, we also determined the ability ol Sp l to bind directly to TAFl 10 in vitro. Biotinylated ohgonucleotides containing Sp l binding sites were coupled to streptavidin-agarose resin. The resin was incubated ith Sp l that had been over-expressed and puπfied from HeLa cells intected with a vaccinia virus expression vector (Jackson et al., 1990). After allowing Sp l to bind DNA on the beads, the unbound Spl was washed away. Control resin that lacked Spl was also prepared and tested in parallel. These resins were incubated in batch with S-labeled TAFl 10 synthesized in vitro in a reticulocyte lysate After incubation with the labeled protein, the beads were extensively washed and the bound proteins were eluted in two steps with buffer containing 0 2 M KCl loliowed by 1.0 M KCl. The 1.0 M salt incubation elutes Spl from the DNA ' 1 he input, unbound supernatant, and eluted fractions were subsequently analyzed by SDS-PAGE and autoradiography. Samples from the binding reaction were also analyzed by silver staining to detect non-specific binding of proteins present in the reticulocyte lysate. 3< S-labeled TAF l 10 synthesized in vitro in a reticulocyte lysate and incubated with streptavidin-agarose beads with or without DNA-bound Spl . Protein fractions were run on SDS-PAGE and analyzed by autoradiography or by silver staining. After allowing TAFl 10 to bind Spl , the beads were pelleted and the supernatant containing the unbound proteins was collected. The resin was washed 4 time. The specifically bound proteins were eluted by incubating the beads in buffer containing 0.2 M KCl. followed by 1.0 M KCl. The Spl protein bound to the DNA is eluted by treatment w ith 1 .0 M salt. Labeled TAFl 10 protein is detectable in the eluted tractions No detectable TAFl 10 protein bound to the DNA affinity resm in the absence ol Spl protein. Quantitation of these results by analysis of the gel in a Phosphorlmager (Molecular Dynamics) indicate a 60-fold greater binding by labeled TA F l 10 to the Spl -containing resin. The silver stained gel showed that Sp l is the nι.i|or species in the eluate indicating that the unlabeled proteins the extract are not able to bind Sp l . These data show that 1 AF 1 10 is selectively retained on the resm containing DNA-bound Sp l . but ' I \ E 1 10 does not bind the control resin that lacks Spl . Most of the bound TAF l 10 elutes with the Sp l at 1.0 M KCl with a lower amount eluting at 0.2 M KCl. Analysis of the tractions by silver staining indicates that Spl is the ma)or protein detectable in the high salt eluate, indicating that the 23 unlabeled proteins present the reticulocyte lysate. which constitute the vast majority of the total protein in the input, are not non-specifically binding to Spl in this assay. To rule out the possibility that an intermediary protein, perhaps some other TAF or other eukaryotic protein, was required for the Spl-TAFl lO interaction, this experiment was repeated using ^S-labeled TAFl 10 synthesized in an in vitro transcription/translation extract derived from E. coli (Skelly et al., 1987). The TAFl 10 protein synthesized in the prokaryotic system was also specifically retained on the Spl affinity resin providing further evidence that Spl can bind directly to TAFl 10. As an additional test of specificity, we also determined if deletion mutants of TAFl 10 could bind to Sp l in this in vitro assay (mutants are expressed from the N-terminal). A 1 - 137 mutant was not able to bind Spl in vitro, while some binding was obtained w ith a 1 -308 mutant. Mutants of 308-921 , 447-921 , and 571-921 were all effective binding Spl , while C-termina deletions beyond 852 from these mutants eliminated Sp l binding. These results indicate the importance of a 852-921 region and a 137-308 region of TAFl 10 in transcription activator interaction. TAFl 10 does not directly bind TBP Our experiments indicate that TAFl 10 cannot directly bind to TBP by itself and that at least one additional TAF is required to connect TAFl 10 and TBP. For example, α-TAF l 10 antibodies fail to coprecipitate both in vitro expressed TAFl 10 and TBP and similarly with -TBP antibody. Exemplary Experimental Procedures Purification of the TFII complex For the in vitro transcription assay, the TFIID complex was immunopurified from the partially purified TFIID fraction (Q-sepharose fraction, 0.3 M KCl eluate) (Dynlacht et al .. 1991 ) using the α-dTBP monoclonal antibody 42A11 coupled to protein G-sepharosc (Pharmacia). The immunoprecipitates were washed with 0. 1 M KCI-HEMG-ND buffer (25 mM HEPES pH 7.6, 0.1 mM EDTA, 12.5 mM MgCl ,. 10% glvcerol, 0. 1 % NP-40. 0. 1 mM DTT) and the TFIID complex was eluted from the antibody by addition 10 mg/ml of the peptide 24 mimicking the epitope of 42Λ 1 1 (sequence: NH2-RPSTPMTPATPGSADPG- COOH) in HEMG buffer containing 0.5 M guanidine-HCl. The eluate was dialyzed against 0. 1 M KCI-HEMG-ND. and then assayed for transcription activity. Purification of dTΛF I 10 Nuclear extracts derived from approximately 1 kg of Drosophila embryos were prepared and fractionated as previously described (Dynlacht et al., 1991; Wampler et al., 1990). For protein sequencing, the TFIID complex was purified with polyclonal α-dTBP antibodies as previously described (Dynlacht et al., 1991) or with a monoclonal antibody as described above. The TAFs were separated from TBP by elution of the protein Λ-antibody resin with 0. 1 M KC1-HEMG buffer containing 1.5 mM DTT. 0. 1 % LDΛO (lauryl dimethylamineox.de), and 1M Gd- HC1. The TAFs were eluted by batch incubation of the resin with an equal volume of buffer for 25 min at 4 "C. This procedure was repeated and the two supematants were combined. Urea was added to 8 M, DTT to 10 mM, and cysteines were modified with 4-vinylpyridine. Two approaches were used to separate the TAFs: HPLC and PAGE. Under the HPLC approach, the TAFs were fractionated by reverse phase HPLC on a 300 angstrom C4 column (2. 1 X 30 mm). The proteins were eluted with a gradient from 20-70% buffer B (buffer A = 0. 1 % TFA, 1 % n-propanol; buffer B = 0.1 % TFA, 1 % n-propanol. 60% isopropanol, 30% acetonitrile). TAFl 10 consistently eluted at }5 '7r buffer B. Fractions containing TAFl 10 (approximately 5 μg) were lyophilized. resuspended in 100 mM TRIS, pH 8.0, and 2 M urea, and incubated at 55 "C for 10 min. 150 ng of the protease lys C was added and the protein was digested for 20 hr at 37 "C. Peptides were chromatographed and sequenced as previously described (Williams et al., 1988). Under the gel electrophoresis approach, the TAFs were separated by electrophoesis and transferred to membranes. The separated TAFs were digested with LysC or trypsin and the resultant peptides eluted, chromatographed and sequenced. See Fernandez et al.. ( 1992) Analytical Biochemistry 201 , 255-264. In vitro transcription assay Transcription factor tractions were reconstituted with basal factor fractions derived from 0- 12 hr Di osoplula embryo nuclear extracts essentially as previously described (Dynlacht et al.. 19 1 ) except that TFIIB was separated from TFIIE/TFIIF and pol I I w as tractionaied further on a phosphocellulose column. Each reaction contained 0.5 ug ot the TFIIB fraction (S-sepharose 0.5 M eluate), 1.5 ug of the TFIIE/TFI I F fraction (S-sepharose 0.25 M eluate), and 0.25 mg of the pol II fraction (phosphocellulose 0.4 M eluate). Some reactions contained 1.5 ug of the TFIID traction or 2 ng of purified, recombinant dTBP that had been expressed in E. coli ( Hoev et al. , 1990). The template for the in vitro transcnption reaction was BCΛT (Eillie and Green, 1989) containing 3 Spl binding sites, and transcription was assayed bv primer extension. Generation of antibodies against the TAFs Immunopurified TFI ID complex (approximately 10 ug/ injection) was mixed with Ribi's adμivant and iniected mtraperitoneally into a Swiss-Webster mouse at days 0, 7, and 2 1 . The initial immune response was monitored at day 28 and boosted further by two biweekly injections of more antigen. After an intravenous injection ot one further dose of antigen the spleen was dissected out and electrofuscd with myeloma cells. Approximately 600 supematants from 96-well dishes (each well containing on average 5 independent hybπdomas) were assayed on western strip blots lor cross-reactivity with immunopurified TFIID complex proteins. Hybπdomas f rom w ells producing anti-TAF and/or anti-TBP antibodies were cloned by limited dilution and tested by Western blotting and immunoprecipitation assays. Cloning of TAF l 10 cDNAs The polyclonal antiserum obtained from the immunization scheme described above was used at a 1 / 1000 dilution to screen approximately Sx lO 1 plaques of a size-selected ( > I 8 kb) s>- 12hr Igt l 1 Drosophila cDNA library (Zinn et al. , 1988). Positive clones w ei e placiue-puπlied to homogeneity and tested for cross- reactivity against anti-TA I monoclonal antibodies of known specificity. One clone, X106, cross-reacted strongly w ith several independent anti-TAFHO hybridomas. Insert DNA (2.6 kb) I ron, λ 106 was purified and labeled using Klenow polymerase and random hexamei pi nning (Λmersham). lO'' recombinant phage from a cDNA lιbrar\ ( Poole. et al . 198^ prepared from 3-9 hour Drosophila embryos were screened as pieviouslv described ( Kadonaga et al. , 1987). 24 positives were obtained in duplicate on the primary screen; 12 of these were randomly selected tor rescreening, and 10 ot 12 were positive on the secondary screen. All 10 of these cDNA clones were found to be related to each other on the basis of restriction mapping and cross-hybridization. The largest cDNA clone of 4.6 kb, λl 10-5, was completely sequenced, and two other clones of 3. 1 kb, λl lO- 1, and 2. 1 kb. λl 10-2. were partially sequenced. The inserts were subcloned into pBS-SK (Stratagene) in both orientations, a nested set of deletions was constructed with exonuclease II I. and the clones were sequenced by the dideoxy method. The XI 10-1 clone was found to be 37 nucleotides longer at the 5' end than the λl 10-5 clone and missing 1.5 kb on the 3 ' end. The SEQUENCE ID NO: 1 is a composite of the λ l 10- 1 and λ l 10-5 sequence. Expression of dTΛF l 10 protein An Ndel site w as created at the initiating methionine using a PCR based strategy. A 3. 1 kb Ndel-BssHII fragment containing the entire coding sequence was subcloned into the Smal site of the baculovirus expression vector pVL1392 (Pharmingen). Recombinant baculoviruses were selected by co-transfection of Sf9 cells with the expression \ ector and linear viral DNA as described by the supplier (Pharmingen). Samples lor the w estern blot were prepared by infecting SF9 cells with recombmant virus obtained I rom the transfection supernatant. Three days after infection the cells w eie harvested, washed, resuspended in HEMG buffer, and lysed by somcation. I he pi otein concentration was measured by Bradford assay. After electrophoresis proteins were transferred to nitrocellulose: TAFl 10 protein was detected using the monoclonal antibody 3E7 Transfections Transfection ol Schneider cells (line SL2) was carried out as previously described (Courev and Tpan. I OXX) except that the transfections were performed in 60 mm dishes. The expression vector tor all proteins used in this study was pPac, 27 which contains the Drosophila actin 5c promoter. TAF l 10 sequences were fused in frame to GAL4 DNA binding domain, residues 1- 147. The following restriction fragments of the TAF l 10 cDNA were used: N 1 7. Ndel-Clal; N308. Ndel-Sall, 138-308, Clal-Sall; 87-308. H ind i . The constructs were checked by sequencing across the fusion junctions. The amounts of DNA used were as follows: 100 ng of the pPacGAL4 derivatives. 500 ng of the pPacSpl N539, and 2.5 ug of the reporter gene pG5BCAT (Eillie and Green. 1989). CAT assays were performed and quantitated as previously described (Courey and Tjian, 1988). Yeast Methods The yeast strain Y I 3 (a. gal4, ga!80, his3, trpl-901 , ade2-101 , ura3-52, leu2-3, 1 12, URA3: :( ial l : lacZ. EYS2: :Gal-His3) was transformed with two plasmids according to the method of Shiest! and Gietz (Schiestl and Gietz, 1989). The Gal4 DNA binding domain hybrids were constructed in the vector pAS l. pASl is a 2μ plasmid with TI .P selection that expresses fusions to Gal4(l-147) from the ADH promoter. For expression of GAL4( 1- 147), an Xbal linker containing stop co ons in all three reading frames was inserted in pASl immediately downstream of the GΛL4( 1 - 147) coding sequence. G4-1 10 (fl) contains the entire coding region of the TAF l 10 on an Ndel-BssHII fragment, and the shorter G4- 1 10 fusions contain fragments as described for the Drosophila expression vectors. G4-80 ( II) contains an Ndel-Xbal fragment that includes the entire coding region ol ' Drosophila TΛF80. G4-40 (fl) contains an Ndel-EcoRV fragment encoding Drosophila TΛF40. G4-dTBP( 191 C) contains an Ndel fragment derived from pΛR- 1 I C containing the conserved C-terminal domain (Hoey et al., 1990). The reading frame across all fusion junctions was verified by sequencing, and the protein expression was verified by western blot analyses with either α-TΛF or π -GΛ I .4 antibodies, with the exception of G4- 1 10(N137). The acidic activation domain fusions were constructed in the vectors pGADlF, pGAD2l : or pGΛ D3F which differ only in the reading frame of a unique Bam site (Chien et al.. 1A 1 ). These 2μ plasmids with LEU2 selection express fusions to activating region I I ( residues 768-881 ) of GAL4 from the ADH promoter. Sp l region A consists of amino acids 83-262 and Spl region B consists of residues 263-542: these were cloned as BamHI-Bglll fragments from the 28 plasmids pKSAB lO and pKS G lespectively The C-terminal 100 amino acids of CTFl (residues 399-449) were cloned as a Bglll-EcoRI fragment (Mermod et al. , 1989). The Antp construct w as made by subcloning a Bam HI fragment containing the activation domain (Courev et al , 1989) Bed residues 249-489 (Dπever et al. , 1989) were cloned on a Sai l I ragment derived from pPac-bcd. The reading frame across all fusion junctions w as veri fied by sequencing. Transformed yeast w eie assayed qualitatively after growth on media containing X-gal. Quantitative l.-galactosidase assays were performed as descπbed (Himmelfarb et al. , 1990) except cells were grown to mid log in selective media containing 2 % glucose Assays w ere performed in triplicate and activity is expressed as units/mg of total protein In vitro protein-protein interaction assay A 3. 1 kb Ndel-BssHll f ragment containing the entire TAFl 10 coding region was subcloned into the plasmid pTbSTOP (Jantzen et al. , 1992), which contains the b-globin untranslated leader downstream of a T7 promoter. The plasmid was linearized with Xbal, and the gene was transcribed in vitro with T7 RNA polymerase. Αinet labeled protein was synthesized in vitro in a rabbit reticulocyte lysate (Promega) Alternatively, TAF l 10 was synthesized in vitro in an E. coli derived S30 transcription/translation extract (Skelly et al. , 1987). Spl protein was ovcrexpressed in HeLa cells using a vaccinia virus expression vector (Jackson et al.. 1990) and puri f ied by wheat germ agglutinin (WGA) affinity chromatography ( lackson and Tjian 1990), prior to DNA affinity purification as outlined below. DNA altmity res w as pi epared as follows: 5'-bιotmylated ohgonucleotides containing 4 Sp l binding sites. GCA(AGGGGCGGGGCT) T and its complement, were annealed and coupled to streptavidin-agarose beads (Pierce) by incubating overnight at room temperature. The beads were incubated with WGA-puπfied Spl in but lei /. ' (25 mM HEPES, pH 7.6, 20% glycerol, 0. 1 % NP-40, 10 mM ZnSO,. I mM DTT) containing 0. 1 M KCl for 2 hours at 4 °C. Spl was bound to the res at a concentration of approximately 1 mg/ml of beads. 35 S-labeled TAFl 10 w as incubated in batch with 15 ml of the DNA affinity resin in Z' - 50 mM KCl . w ith oi w ithout Sp l lor 4 hours at 4 °C. The beads were 29 washed 4 tunes with I ml ol the same bul ter, and eluted with Z' + 0.2 M KCl, followed by Z ' + 1 .0 M KCl . I he eluted proteins were TCA-precipitated and analyzed by SDS-PΛGE. I .eiore autoradiography. the gel was fixed and treated with Amplify (Amersham ). Detection of Direct TBP/TΛF Interactions on Protein Blots Immunopuπfication ol the Drosophila TFIID complex using anti-TBP antibodies results in the purification of a large muitiprotein complex consisting of TBP and 7 major TAFs. To identify TAFs which can bind directly to TBP we probed a blot containing renatured TAFs with a 32P-labelled TBP-GST fusion protein. After washing oi l unbound TBP- usion protein and exposing the blot to X-ray film a strong signal was seen which coincided with the position of dTAFII-250K on the gel. Further experiments revealed that a truncated version of TBP, consisting of the highly conserved C-termmal domain, is sufficient to mediate this interaction. We also tested other tractions containing basal factors (Wampler et al., 1990; Dynlacht et al .. 1991 ). including TFIIB, E/F and RNA polymerase II, and failed to detect specific signals. We conclude that TBP and TAFII-250K interact directly and that TAFI I-250K is present in the TFIID fraction but not associated with TFIIB, E, F or RNA polymerase II. Molecular Cloning and Characterization of the dTAFH-250K Gene Having identified dTΛEII-250K as a candidate for a direct TBP-TAF interaction we decided to clone the corresponding gene. The low abundance and large size of dTAF(I I)-25()K disiavours cloning strategies based on protein microsequencmg. Instead, w e were able to obtain monoclonal antibodies which specifically (and exclusively) recognize dTAF(II)-250K on Western blots. To show that dTAF(II)-250K is indeed a genuine component of the TFIID complex, we used two of these monoclonal antibodies. 2B2 and 30H9, to carry out immunoprecipitations iron, the TFI ID traction. The pattern and stoichiometry of TAFs and TBP is indistinguishable Irom the ones described previously using either anti-TBP (Dynlacht et al .. 199 1 ) or anti- dTΛF(II)- l 10K (Hoey et al. , 1993) antibodies. We cloned the gene encoding the Drosophila dTAF(II)-250K by screening a lgt l 1 expression library prepared from 6- 12 hour old embryos (Zinn et 30 al., 1988) with hybπdonia supematants containing either 2B2 and 30H9 anti-dTAF(II)-25()K monoclonal antibodies. Five partial cDNA clones were obtained, which all cross-hvbπdized with each other at high stringency. Restriction mapping and sequence analysis confirmed that they were indeed derived from the same gene. Two ot these cDNAs. ID- 1 and 1D-2, allowed us to establish a composite open reading I rame spanning 4.5 kb (fig. 2). Attempts to isolate additional cDNA clones encoding N -terminal regions of dTAF(II)250 or 5'-RACE experiments have so tar been unsuccessful. Genomic DNA sequencing allowed us to extend the open reading frame by approximately 1 kb before encountering noncoding (presumanblv intronic) sequences. Inspection of the open reading frame encoded by the cDNA clones reveals a protein sequence which displays an extensive similarity to the human ' Cell Cycle Gene I ' (CCG 1) gene previously described by Sekiguchi et al.. 19 1 . Many of the sequence elements defined in the CCG1 genes arc also present in the dTΛF-250K encoding sequence. Interestingly, however, we detected a 35 amino acid insertion in the region which Sekiguchi et al. putatively identified as an HMG box. This insertion causes substantial disruption of the spatial alignment with the consensus sequence. We also used the 1D-2 cDNA fragment to map the dTAFII-250K gene to position 32E1-2 (left arm of chromosome II) by in situ hybridization. This location does not contain any previously characterized genes and currently no deletions spanning that regions are available. Since dTΛF-250 seems to be present in all or the majority of the TFIID complexes present within cells and seems to provide essential contact points with TBP and TAFs (see below) w e expect that a deletion of the 32E1-2 locus would cause a lethal phonoiype. Expression of the ( ' -terminal domain of dTAF(ll)-250K in Insect Cells To study the liinctional properties of the proteins encoded by these cDNAs we decided to express the protein encoded by the reading frame of our longest cDNA, 1D- 1. Because ol the expected large size of the protein encoded we chose the baculovirus system. After subclonmg of the fragment into expression vector pVL1393 and transtecting the construct into Sf9 cells we detected expression of a 180K protein (subsequently rei erred to as DN250) which cross-reacted strongly with several anti-TΛ I A) monoclonal antibodies recognizing a variety of epitopes 1 in different parts ot the 2^()K T \F. We detected no cross-reactivity between our antibodies and any endogenous Sj.odoptera TAF250 homologs which might be present in Sf9 cells. The C-terminal Domain of the dTΛF(l l)250K Is Sufficient for TBP Binding To study whether DN250 was capable of interacting with TBP we immunopurified the protein irom mlected cells. Monoclonal antibody 30H9 was bound to protein A or G beads and incubated with extracts from baculovirus infected cells. Under these conditions DN250 is specifically immobilized on the beads. After washing oi l unbound material we added an extract containing partially purified TBP (also expressed in the baculovirus system). TBP was specifically bound to beads carrying the immunopurified TAF250-C180 protein whereas beads containing antibody only failed to do so. Further evidence for this direct TBP-TAF interaction by carrying out protein blots. The ability of a protein representing appr. 60% ol ' the full-length 250K protein to bind TBP demonstrates conclusively that the cloned C-termmal part is sufficient for TBP binding. Gelshift Analysis of the DN250/TBP Complex TBP is the only component of the general transcriptional machinery capable of sequence-specific binding to the TATA box. We therefore were interested to see how interaction of TBP with TAF250-C 180 affected the specificity and affinity of DNA binding. TBP was added to a 32-P labelled DNA fragment containing the -33 to +55 region ol the adenovirus maior late promoter and DNA-binding was monitored using a gelshitt assay. The intensity of probe DNA shifted by TBP increased substantially in presence ol purified TAF250-C180 wheras TAF250-C180 alone did not dctectably bind to DNA. To investigate whether this enhanced affinity of the TBP/TΛF250-C I 80 complex for DNA was due to additional contacts with DNA provided by the TΛF250-C 180 protein we carried out footprinting studies, again using the adenovirus maior later promoter region as a probe. TAF250 and TA F l I P Speci f ical ly Interact With Each Other, even in Absence of TBP Since we have not observed any of the cloned Drosophila TAFs to bind to TBP we investigated whether they would interact with the TBP/ d250KdeltaC180 complex. 35S-labelled 1 10K protein (Hoey et al., 1993) was synthesized in an in-vitro translation system anil incubated with TAF250-C 180 protein in presence and absence of TBP. As shown in fig. 5 we found that the 1 10K TAF binds specifically to dTAF(II)250K-C 180 in the presence and absence of TBP thus indicating that the two proteins bind independently to two distinct domains within the 250K TAF. The affinity and specificity of this interaction is sufficiently high to allow selective purification of TAFl 10 from a crude baculovirus extract expressing the recombinant protein by using TAF250-C 180 immobilized on beads. Protein Blot Analysis pGEX-2TK was linearized with Smal, phosphatase-treated and the ligated with gel-purified Nile! fragments of either pARdTFIID or pARdTFIID-191C (Hoey et al., 1990). Generation of 32-P labelled GST fusion protein, protein blotting and hybridization were carried out essentially as described in Kaelin et al., 1992. Generation of anti-dTA FI I-250K Hvbridoma Cell Lines The monoclonal antibodies described in this study were derived as described in Hoey et al.( 1993). Briefly, a Swiss-Webster mouse was immunized with intact immunopurified Drosophila TFIID complex. After fusion hybridoma supematants containing anti-dTΛFII-250K antibodies were selected using stripblots containing SDS-gel-se|)arated TBP and TAFs. Two such cell lines, 2B2 and 30H9, were then cloned to homogeneity by limited dilution. Isolation of dTAFII-25()K cDN'A and Genomic Clones Approximately x 1 ^ independent plaques of a size-selected ( > = 1.8kb) Drosophila Igt l I library prepared I rom Drosophila embryos (Zinn et al., 19..) were screened with two independent antι-dTΛFlI-250K monoclonal antibodies, 2B2 and 30H9. All the posiuves identi fied cross-hybridized at high stringency with each other on the DNA level . Restriction mapping and sequence analysis showed that all 3 of the clones were derived i rom the same gene. cDNA clones 1D 1 and 1D2 contained inserts ol 1 .5 and 4.0 kb. res|")ectιvely. and were sequenced to completion. 1D2 was found to extend 500 bp further towards the 5' end of the gene and was used to isolate genomic clones IDASH3 and 1DASH4 (Sau3A partially digested DNA cloned into I DASH ). Sequencing Strategy We employed the gd transposon-directed sequencing strategy (Gold Biosystems) as described in Strathmann et al. , 1991. DNA fragments of interest were subcloned into the plasmid vector pMOB l and electroporated into DPWC cells. After conjugation with the recipient host BW26 the mixture was plated out on kanamycin/carbenicillin plates. Transposon insertion points were mapped by PCR. Clones with the desired transposon locations were then grown up and sequenced using transposon-speci fie primers with 35S-dATP or the Pharmacia A.L.F. Sequencer. Expression of a Truncated Version of (ITAFII-250K (DN250) in the Baculovirus Svstem cDNA #5 was inserted into the EcoRI site of Baculovirus-expression plasmid pVL1393 (Pharmingen). The resulting construct was co-transfected with 'BaculoGold' viral DNA ( Pharmingen) into Sf9 cells. After 3 days cells were harvested and expression of the DN250 protein was monitored by Western blotting using the anti-dTΛ FI I-250K monoclonal antibody 2B2. The recombinant virus-containing supernatant w as used to infect large scale cultures of Sf9 cells. We typically prepared whole cell extracts from 1 liter of plate cultures of infected Sf9-cells by sonicating them in HEMG-ND/0. I M KCl (HEMG-ND contains 25mM HEPES. pH7.fi. mM M«(T2 0. 1 mM EDTA. 0. 1 % NP40, 1 mM PMSF, 1.5 mM DTT. 5mg/ml leupeptin ). The supernatant was partially purified (approximately 5 fold ) by chromaiography over Q-sepharose (Pharmacia) with step gradient elution (HE.MC i containing 0. 1 M, 0.2. 0.4 and 1.0 M KCl, respectively). dTAFII-250K(C 180) eluted in the 0.4 M stepfQ.4' fraction). After dialysis against HEMG-0. I M KCl the extract was f rozen in aliquots and used for the immunopurification/coprecipiiation studies. 34 Coimmunopreciptiation Studies Protein G-beads w ere preloabded with monoclonal antibodies and incubated with various cell extracts l m Baculovirus-mfected cell tractions or 35S-labelled dTAFIIl 10 prepared b\ in vitro translation After 45 minutes on ice, unbound protein was removed w ith several washes with HEMG-ND. hTAFII250 purification and cloning We previously reported the isolation of hTFIID by affinity chromatography using antibodies specific to TBP The purified complex contains at least seven distinct TAFs ranging in molecular weight from 30-250 kD which copuπty with TBP. We were particularly interested in characterizing the 250 kD species because this subunit of TFIID appears to bind TBP directly as determined by Far Western analysis. Using al l inity-puπiied TAFs to immunize mice, we generated both polyclonal and monoclonal antibodies that crossreact with different TAFs. We used these antibodies to screen Igt l 1 expression cDNA libraries and several clones were isolated, including IH I which contains a 1.1 kb insert. To determine which, if any, TAF is encoded by IH I , we expressed this cDNA as a GST fusion protein, purified the tagged protein by glutathione affinity chromatography, and raised antibodies against this recombinant protein. Antisera directed against GST-1H1 specifically crossrcacted with the 250 kD TAF, indicating that a portion of the gene encoding I.TΛFI I250 had been isolated. Next, we determined the DNA sequence of IH I and discovered that this open reading frame is related to the |.revιouslv identified human gene, CCG1, which had been implicated in cell cycle regulation. Specifically, a temperature-sensitive mutant hamster cell line, is 13, is arrested at G l a few hours before entering S phase at the non-permissive temperature. Expression of human CCG1 m ts l 3 overcomes this cell ι \ cle block. Since IH I only encoded a small portion of I.TAF1 I250. w e isolated several additional clones from a primary HeLa cDNA library, including I H2. w hich contained a 5.3 kb insert. The construction of a full-length hTΛFII250 cDNA revealed the predominant hTAFII250 RNA species characterized in Hel .a cells encodes 2 1 additional amino acids between residues 177 and 178 relativ e to CCG 1. Interestingly, we sequenced several other cDNAs containing internal insertions oi deletions when compared to CCG 1. This finding suggests that multiple hTΛFII250-related proteins may be generated by alternate splicing of a primary transcript. Although the finding that a cDNA isolated by antibodies directed against TAFs encodes a cell cycle gene is exciting, it was important to provide some functional evidence that this clone indeed encodes a bona fide TAF which is a subunit of TFIID. We first asked whether the recombinant hTAFII250 expressed in a vaccinia virus system becomes associated with the endogenous TFIID complex in HeLa cells. To distinguish between the recombinant and endogenous protein, we engineered a version containing a hemagglutinin antigen (HA) epitope at the N-terminus of hTAFII250. Antibodies against TBP were used to immunopurify the TFIID complex from HeLa cells infected with either recombinant or control vaccinia virus. The immunopurified complexes were subjected to gel electrophoresis and analyzed by Western blot analysis using either a monoclonal anti-HA antibody to detect the HA-tagged molecule or monoclonal antibody 6B3, raised against the endogenous I.TΛFII250. The anti-HA antibody crossreacted specifically with a 250 kD protein only in the TFIID complex prepared from recombinant hTAFII250 virus infected HeLa cells but not control infected cells. As expected, 6B3 recognized both the recombinant hTAFII250 and the endogenous protein. Thus, we conclude that the recombinant hTAFII250 associates with TBP in vivo and is part of the TFIID complex. To test for a direct interaction between hTAFII250 and TBP, we performed a Far Western analysis with radiolabellcd TBP and antibody immunopurified HA-tagged I.TAFII250. The full-length hTAFII250 is capable of interacting directly with TBP in vitro, even in the absence of other TAFs or coactivators. These results and the analysis of the independently cloned Drosophila TAFII250 suggest that this largest TAF is responsible for the initial assembly of the TFIID complex by binding directly to " EBP and other TAFs. The important role of I.TΛFII250 in the formation of a TFIID complex prompted us to define more precisely its interaction with TBP. For these studies we employed the two hybrid system carried out in yeast cells. Using this rapid and convenient assay for protei protein interactions, we observed that a hybrid construct containing hTAFII250 fused to the DNA binding domain of GAL4, G4(l-147), interacted selectively and efficiently with human TBP attached to the 36 acidic activation domain of GAE4. (54(768-881 ). Yeast expressing both of these proteins produced high levels of b-galactosidase due to increased transcription of a lacZ reporter construct, containing GΛL4 binding sites. Interestingly, hTAFII250 also interacts efficiently with a truncated version of human TBP which contains only the conserved C-terminal 180 amino acids. By contrast, a construct containing the "species-specific" N-terminal domain of human TBP failed to interact with hTAFII250. These results are in agreement with Far Western experiments using radiolabelled cTBP and nTBP as probes and suggest that residues 160 to 339 on the outer surface of TBP may be responsible for hTAFII250 binding. Our unexpected finding that hTAFII250 is related to CCG 1 suggests a rather intriguing link between a subunit of TFIID and expression of genes involved in cell cycle control. Interestingly. CCG 1 is a nuclear phosphoprotein with several domains characteristic ot ' transcription factors including a putative HMG-box and a proline-rich cluster. Based on these structural motifs, Sekiguchi et al. suggested that CCG1 might work as a sequence-specific transcription factor needed for regulating genes involved in the progression through G l . However, it now seems clear that CCG 1 or a related product is part of the TFIID complex and is not a promoter-specific transcription factor. Therefore, it seems more likely that the Gl arrest in tsl3 is due to the failure of a defective TFIID complex to mediate activation by a subset of cellular transcription factors that govern cell cycle genes, e.g. thymidine kinase and dihydrol ' olate reductase genes. The presence of a putative DNA binding domain, the HMG box, may suggest that once hTAFII250 forms a complex with TBP. some portion of this large subunit of TFIID may contact DNA, perhaps downstream of the initiation site. Immunoaffinity purified hTEl l D complex: Interaction with hTBP and production of hTAFs-specific antibodies A. Immimoprecipiiaiion reactions were carried out according to a modified version of previously described procedures (Tanese et. al.). 0.5 mg of affinity purified a-hTBP antibody was added to 200 mg of hTFIID (phosphocellulose 0.48 - 1.0 M KCl) fraction, and the mixture nutated for 2 - 4 hrs at 4oC. Protein A Sepharose was then added and nutation continued for an additional 2 - 4 hrs. 37 Antibody-antigen complexes were pelleted by low-speed centrifugation, washed four times with 0. 1 M KCl - HEMG (25mM Hepes, 12.5 mM MgC12, 0.1 mM EDTA. 10% glycerol ) containing 0. 1 % NP-40 and I mM DTT. The immunoprecipitated hTFIID complex was subjected to 8% SDS-PAGE and silver stained. For Far Western analysis, the proteins were blotted onto nitrocellulose membrane and hybridized with 35S-labeled hTBP (Kaelin et al.). pTbhTBP was used to in vitro transcribe hTBP RNA which was in vitro translated using 120 Ci 35S-methionine ( > 1000 Ci/n.Mol. Amersham) in reticulocyte lysate (Promega). B. Antigen used to immunize mice for antibody production was prepared as follows. The immunoprecipitated hTFIID complex, purified from 250 litres of HeLa cells, was eluted from the Protein A Sepharose - antibody complex with 0.1 M KCl - HEMG containing I M guanidine - HC1, 0. 1 % NP-40, and 1 mM DTT. Under these conditions TBP remained bound to the antibody. The eluted TAFs were dialized against 0. 1 M KCl - HEMG containing 0. 1 % NP-40 and 1 mM DTT. The mixture of proteins containing 1 -2 mg of each TAF was used to immunize a mouse. Test bleeds were taken and the immune response monitored by Western blot analysis. After a series of five boosts, the mouse was sacrificed and the spleen was used f r the production of monoclonal antibody producing hybridoma cells lines. The identification of hybridoma cell lines producing hTAF specific antibodies was determined by Western blot analysis of eluted TAFs. Cloning and identification ol the 250 kD subunit of hTFIID complex as CCG1 A. An expression screen of 2.4 x 106 PFU from a lgtl l HeLa S3 cDNA library (Clontcch) was carried out using the a-hTAFs polyclonal serum described above. 38 primary signals w ere identified of which 6 were plaque purified. 1 phage DNA was prepared and analyzed by EcoRI restriction enzyme digestion. IHI contained a 1 . 1 kb insert which was subcloned into the EcoRI site of pGEXl (Pharmacia) to express a GST-IH 1 fusion protein. The resulting construct was transformed into Escheπchia coli TG2, and following induction with 0.5 mM IPTG, the induced protein was purified on glutathione Sepharose 4B beads (Pharmacia). 2 mg (per miection ) of the fusion protein was used to immunize a mouse. Test bleeds were taken and used for Western blot analyses. 38 B. Poly(Λ)+ RNA from HeLa cells was used for construction of a directional cDNA library in 1ZΛPII (Stratagene) as described previously (Ruppert et al. 1992). Using a randomly 32P-labeled probe derived from the IHI cDNA insert, 15 independent cDNA clones were isolated from 1.2 x 106 original PFU. The cDNA inserts were rescued by the zapping procedure (Short et al.) and characterized extensively by restriction enzyme analysis and Southern blotting. The longest cDNA clone isolated from 1H2 contains a 5.3 kb insert, revealing an extended 3' untranslated region but missing about 1.15 kb of 5' sequences when compared to CCG 1. This 5' region was generated by PCR using conditions described previously (Ruppert et al.). Two set of PCR primers were designed according to the CCG 1 cDNA sequence (Sekiguchi et al). PCR-I, forward primer #1: 5'-TATTTCCGGCATATGGGACCCGGCTG-3' (position 40 to 65, containing an engineered Ndel restriction site at the translation start codon) and reverse primer #2: 5'-GAAGTCCACTTTCTCACCAG-3' (position 578 to 597). PCR-II, forward primer #3: .S'-TΛCCΛGCAGCΛTΛTGGGGAGCTTGCAG-S' (position 421 to 447) and reverse primer #4: 5'-GCTCTAAGGAAGCCAGCCTGCCAGGCTTG-3' (position 1343 to 1371). All PCR products were subcloned into pBluescript KS (Stratagene) and sequenced. The most abundant product of PCR-II, a 1 kb fragment, included a 63 bp in frame insertion , while a minor 330 bp fragment revealed a 618 bp in frame deletion with respect to the CCG 1 cDNA. To generate a full-length hTAFII250 cDNA, the product of PCR-I and the I kb PCR-II product were joined via the shared Smal restriction site. Subsequently the 1.2 kb Xbal fragment of the resulting plasmid was cloned into Xbal cut pH2 to generate the full-length cDNA clone phTAFII250. Analyses of I.TAFII250 and hTBP interaction A. To construct an HA-tagged version of 1.TAFII250 we generated a plasmid, pSK-HAX. containing the hemagglutinin antigen (HA) epitope, factor X cleavage site, and in frame Ndel cloning site. A 6.3 kb Ndel/Asp718 fragment from phTAFII250 was inserted into p K-HAX to generate pHAX-hTAFII250. A 6.0 kb Spel fragment thereof containing the complete coding region of hTAFII250,was inserted into the Xbal site of the vaccinia virus expression vector pAbT4537 (Applied bioTechnology Inc.). Extracts from recombinant virus, 39 vhTAFII250, or control virus ( New York City Board of Health strain of vaccinia virus) infected HeLa cells ( Dynlacht 1989) were fractionated by phosphocellulose chromatography as described (Tanese et al.). hTFIID complexes from the 0.48 - 1.0 M KCl fraction were immunoprecipitated with affinity-purified a-hTBP antibodies, subjected to 8% SDS-PAGE and analyzed by Western blotting. B. To generate an HA-tagged version of 1.TAFII250 in the baculovirus expression system, we first generated new baculovirus vectors, pVL1392HAX and pVL1393HAX, derived from pVL1392 and pVL1393 (Pharmingen), respectively. These vectors contain the HA antigen epitope, factor X cleavage site, and unique in frame Ncol and Ndel restriction sites. A 6.0 kb Ndel/Spel fragment from phTAFII250 was inserted into pVE 1392HAX creating pbHAX-hTAFII250. Whole cell extracts from cither SF9 cells or SF9 cells infected with recombinant baculovirus were prepared in 0.4 M KCl - HEMG (including 0.04% NP-40, 1 mM DTT, 0.2 mM AEBSF. 0. 1 mM NaMBS) and used directly for immunoprecipitation with the a-HΛ antibody. The precipitate was subjected to 8% SDS-PAGE and blotted onto nitrocellulose membrane. The filter was probed first with 35S-labeled hTBP. and subsequently with the monoclonal antibody 6B3. hTAFI!250 interacts with hTBP in yeast hTAFII250, fused to the DNA binding domain of GAL4 (residues 1-147), was constructed by inserting a 6.0 kb Ndel/BamHI fragment derived from pvhTAFII250 into the pASl vector. The activation domain fusions were obtained by cloning inserts into the JIG Λ D I F vector (Chien et al.). The hybird proteins generated included the acidic activation domain of GAL4 (residues 768-881) fused to either full-length . residues 160-339. or residues 1 - 159 of hTBP. The above described constructs were transformed into the yeast strain Y 153 (a, gal4, gal80, his3, trpl-901. adc2- l()l . ura3-52. leu2-3, 1 12, URA3::Gal l :lacZ, LYS2::Gal-His3: as described (Chien et al. ) and b-galactosidase assays performed according to published procedures ( Hoey et al). Drosophila TBP and dT A FH250 interact with the C-terminal portion of dTAFII150 Radiolabeled in vitro translated dTΛFII 150 bound efficiently to immobilized HA-dTBP or dTΛFI I250ΛN (sec Weinzierl et al ( 1993) Nature 362, 511-517). In 40 contrast, dTAFII l 10 and other TAFs failed to interact selectively with dTAFII150, showing that TΛFI I 150 interacts with at least two subunits of the TFIID complex, dTBP and dTΛFII25(). which also contact each other. We also carried out in vivo experiments in which insect Sf9 cells were co- infected with two recombinant baculoviruses, one expressing dTAFII150 and the second expressing either TBP or one of the other TAFs. Complexes were subsequently immunopurified from cellular lysates and analyses by SDS PAGE followed by immunoblotting using antibodies directed against dTAFII150. Coinfection of virus expressing dTΛFII 150 and either HA-dTBP or dTAFII250ΔN resulted in efficient formation and copurification of heteromeric complexes. Similarly, full-length I.TΛFII250 bound efficiently to dTAFII 150. Radioiabeled in vitro translated C-terminal 369 residue portion (dTAFII150ΔN) of this protein binds TBP and dTAFII250ΔN with the same effenciency as the full length protein. No significant binding of a N-terminal 786 residue portion (dTAFII l 50ΔC) was observed: i.e. the interaction interfaces from these proteins are located in the C-terminal |X)rtion of dTAFII150. TSM-1 associates with TBP and TΛFII250 Like dTΛFII 150. TS 1 ΔN (C-terminal 920 residue portion) bound efficiently to yTBP as well as HA-dTBP: hence we conclude that yeast contain a TAFII250 and TSM- 1 is a TAF. The activation domain of the Drosophila regulator NTF-1 (Neurogenic Element Binding Tran.scription Factor- 1 ) interacts with dTAFII150. NTF-1 immuno-copuril.es with dTFIID using anti-dTBP, indicatin that one or more subunits of the dTFIID interacts directly with NTF-1. Using coimmunoprecipitation experiments: dTΛFII 150 was immunopurified from Sf9 extracts containing dTΛFII 150. the immobilized TAF was mixed with recombinant NTF-1, the isolated complex was analyzed by SDS-PAGE, and the presence of NTF-1 was detected by protein immunoblot anaysis, showing that NTF-1 directly interacts with dTΛFII 150. Next we used a GST-NTF- 1 fusion protein containing the N-terminal 284 amino acids of NTF- 1 to bind various truncated bersions of dTAFII150, showing that the N-terminal . but not the C-terminal region of dTAFII 150 bound to the N- 41 terminal extended activation domain of NTF- 1. Neither dTAFIISO nor dTAFII40 bound significantly under these conditions. Using an affinity resin containing a covalently attached synthetic peptide corresponding to the 56 ammo acid minimal activation domain of NTF-1 , we showed that this region is sufficient to interact with dTAFII150 and that the activator interface of dTΛFII 150 is distinct from the C-terminal region with interacts with dTBP and dTΛFII250. Hence, the requirement for TAFs during NTF-1 activation is at least in part mediated by NTF- 1 :dTAFII 150 interactions. TAF Sequence Data Nucleotide and amino acid sequences of: dTAFII30r..(SEQ ID N . I . 22) dTAFU30/_ .(SEQ ID N0:23. 24) dTAFII40 (SEQ I D NO:S. 9) dTAFII60 (SEQ ID NO:6, 7) dTAFIISO (SEQ ID NO:4. 5) dTAFII l 10 (SEQ ID NO: I , 2) dTAF l50 (SEQ ID NO: 19, 20 ) dTAFII250 (SEQ ID NO:3. 14) hTAFII30.v.(SEQ ID NO:28) 1.TΛFII30 USEQ ID NO:27) hTΛFII4() (SEQ ID N :25. 26) hTAFII7() (SE.Q ID NO: 12. 13) hTAFII IOO (SEQ ID NO: 17. 18) hTAFII 130 (SEQ I D NO: 15. 16) hTAFII250 (SEQ ID NO: 10. 1 1 ) hTAFI48 (SEQ ID NO:29. 30) hTΛFI l 10 (SEQ I D NO:31. 32) were obtained as described above. Additional methods relating to Poll TAFs may be found in Comai et al . ( 1992) Cell 68. 965-976. It is evident from the above results that one can use the methods and compositions disclosed herein for making and identifying diagnostic probes and therapeutic drugs. It will also be clear to one skilled in the art from a reading of this disclosure that advantage can be taken to effect alterations of gene expression: both genes encoding TΛF and genes amenable to TAF-mediated transcriptional modulation. Such alterations can be effected for example, using a small molecule drug identified with disclosed TΛF-based screening assays. All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims. 43 SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Tjian, Robert Comai, Lucio Dynlacht, Brian D Hoey, Timothy Ruppert, Siegfried Tanese, Nao o Wang, Edith Weinzierl, Robert O.J. (ii) TITLE OF INVENTION: TATA-Binding Protein Associated Factors, nucleic acids encoding TAFs, and Methods of Use. (iii) NUMBER OF SEQUENCES: $.22. (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Flehr, Hohbach, Test, Albritton & Herbert (B) STREET: 4 Embarcadero Center, 34th Floor (C) CITY: San Francisco (D) STATE: CA (E) COUNTRY: USA (F) ZIP: 94111 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentln Release #1.0, Version #1.25 (Vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: PCT/US9 / (B) FILING DATE: 28-JAN-I99J . (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Osman, Richard A (B) REGISTRATION NUMBER: 36,627 (C) REFERENCE/DOCKET NUMBER: FP57650-2RA0 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: 415-494-8700 (B) TELEFAX: 415-494-8771 (2) INFORMATION FOR SEQ ID N0:1: (i) SEQUENCE CHARACTERISTICS: 44 (A) LENGTH: 4615 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 538..3300 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: CAACTCGTCC GTACCTCGGC GGTCCGTAAA CAATATTTAC TCGGTTTTCG GCTAAATCGC 60 CAGAGAAACG CAACGGGAAA TCGTTTAAAA TGCGCCCCAG TGCACCGAGT TTGAACGCAA 120 AATGAATTGA ATGCTCAACA ATCAGTCCGT GCGAGCACGC GCGAGTGTGT GTGTGCGCAG 180 GAAAACCCGC CGATCGGGAA AAGTGTAGAA AGGCTTAGCG GCGCAAACAA AAGGCAGCGA 240 ATTAGCGAGA TAACACACAC GCGACAACGA CTGCAACGGA TGCGCCAGGA GAAAGGCCGA 300 CGACAGTGAC GGCAAAGGCG AGTGCGAGTG AGCCAGCGCA GCACCAATTC AGCGGAGCAC 360 CCGCTTTTTT GGCCAAGTTC GCTTCTGGAG CGCACAGCAT GCAACAACTC CGCCAACACC 420 AACACAGGAT GTGCGCAACT AGTTGATCGG AACAGGATCG CTCGCCCACA CCAACACACA 480 GAAGTCAGTG GAATAGGAGA AACACACTCG CCAATAACAT AAACACCACA CAGCACG 537 ATG AAC ACC AGC CAG ACA GCT GCC GGC AAT CGC ATC ACC TTC ACC AGC 585 45 Met Asn Thr Ser Gin Thr Ala Ala Gly Asn Arg lie Thr Phe Thr Ser 1 5 10 15 CAG CCG CTG CCC AAT GGC ACC ATC AGC ATA GCC GGC AAT CCC GGC GCG 633 Gin Pro Leu Pro Asn Gly Thr lie Ser lie Ala Gly Asn Pro Gly Ala 20 25 30 GTC ATC TCC ACG GCC CAG CTA CCG AAT ACC ACC ACC ATC AAG ACG ATC 681 Val lie Ser Thr Ala Gin Leu Pro Asn Thr Thr Thr lie Lys Thr He 35 40 45 CAG GCG GGG ATC GGT GGT CAG CAT CAG GGA CTT CAG CAG GTG CAT CAT 729 Gin Ala Gly He Gly Gly Gin His Gin Gly Leu Gin Gin Val His His 50 55 60 GTC CAA CAG CAG CAG CAG TCG CAA CAG CAA CAA CAG CAG CAA CAG CAG 777 Val Gin Gin Gin Gin Gin Ser Gin Gin Gin Gin Gin Gin Gin Gin Gin 65 70 75 80 ACG CAA TCC GCC GGT CAA CCG CTG CTC AAT TCA ATG CTG CCG GCT GGC 825 Thr Gin Ser Ala Gly Gin Pro Leu Leu Asn Ser Met Leu Pro Ala Gly 85 90 95 GTG GTG GTG GGC ATG CGC CAA CAG GCG CCG TCA CAG CAG CAG CAG AAG 873 Val Val Val Gly Met Arg Gin Gin Ala Pro Ser Gin Gin Gin Gin Lys 100 105 110 46 AAT GTG CCC ACC AAC CCG CTC AGT CGC GTG GTG ATC AAC TCC CAC ATG 921 Asn Val Pro Thr Asn Pro Leu Ser Arg Val Val He Asn Ser His Met 115 120 125 GCG GGC GTG AGA CCG CAG AGT CCA TCG ATA ACT TTA AGC ACA CTT AAT 969 Ala Gly Val Arg Pro Gin Ser Pro Ser He Thr Leu Ser Thr Leu Asn 130 135 140 ACG GGT CAG ACC CCG GCA TTG CTG GTC AAG ACG GAT AAC GGA TTC CAG 1017 Thr Gly Gin Thr Pro Ala Leu Leu Val Lys Thr Asp Asn Gly Phe Gin 145 150 155 160 CTG TTG CGC GTG GGC ACG ACG ACG GGT CCG CCG ACG GTG ACA CAG ACT 1065 Leu Leu Arg Val Gly Thr Thr Thr Gly Pro Pro Thr Val Thr Gin Thr 165 170 175 ATA ACC AAC ACC AGC AAT AAC AGC AAC ACG ACA AGC ACC ACA AAC CAT 1113 He Thr Asn Thr Ser Asn Asn Ser Asn Thr Thr Ser Thr Thr Asn His 180 185 190 CCC ACA ACC ACA CAG ATC CGT CTG CAA ACT GTG CCG GCT GCA GCT TCT 1161 Pro Thr Thr Thr Gin He Arg Leu Gin Thr Val Pro Ala Ala Ala Ser 195 200 205 ATG ACC AAC ACG ACC GCC ACC AGC AAC ATC ATT GTC AAT TCG GTG GCA 1209 Met Thr Asn Thr Thr Ala Thr Ser Asn He He Val Asn Ser Val Ala 47 210 215 220 AGC AGT GGA TAT GCA AAC TCT TCG CAG CCG CCG CAT CTG ACG CAA CTA 1257 Ser Ser Gly Tyr Ala Asn Ser Ser Gin Pro Pro His Leu Thr Gin Leu 225 230 235 240 AAT GCG CAG GCG CCA CAA CTG CCG CAG ATT ACG CAG ATT CAA ACA ATA 1305 Asn Ala Gin Ala Pro Gin Leu Pro Gin He Thr Gin He Gin Thr He 245 250 255 CCG GCC CAG CAG TCT CAG CAG CAG CAG GTG AAC AAT GTA AGC TCC GCG 1353 Pro Ala Gin Gin Ser Gin Gin Gin Gin Val Asn Asn Val Ser Ser Ala 260 265 270 GGA GGA ACG GCA ACG GCG GTC AGC AGT ACG ACG GCA GCG ACG ACG ACG 1401 Gly Gly Thr Ala Thr Ala Val Ser Ser Thr Thr Ala Ala Thr Thr Thr 275 280 285 CAG CAG GGC AAT ACC AAA GAA AAG TGT CGC AAG TTT CTA GCC AAT TTA 1449 Gin Gin Gly Asn Thr Lys Glu Lys Cys Arg Lys Phe Leu Ala Asn Leu 290 295 300 ATC GAA TTG TCG ACA CGG GAA CCG AAG CCG GTG GAG AAG AAC GTG CGC 1497 He Glu Leu Ser Thr Arg Glu Pro Lys Pro Val Glu Lys Asn Val Arg 305 310 315 320 ACC CTC ATC CAG GAG CTG GTC AAT GCG AAT GTC GAG CCG GAG GAG TTT 1545 48 Thr Leu He Gin Glu Leu Val Asn Ala Asn Val Glu Pro Glu Glu Phe 325 330 335 TGT GAC CGC CTG GAG CGC TTG CTC AAC GCC AGC CCG CAG CCG TGT TTG 1593 Cys Asp Arg Leu Glu Arg Leu Leu Asn Ala Ser Pro Gin Pro Cys Leu 340 345 350 ATT GGA TTC CTT AAG AAG AGT TTG CCT CTG CTA CGA CAA GCC CTC TAC 1641 He Gly Phe Leu Lys Lys Ser Leu Pro Leu Leu Arg Gin Ala Leu Tyr 355 360 365 ACA AAG GAG CTG GTC ATC GAA GGC ATT AAA CCT CCG CCG CAG CAC GTT 1689 Thr Lys Glu Leu Val He Glu Gly He Lys Pro Pro Pro Gin His Val 370 375 380 CTC GGC CTG GCC GGA CTC TCT CAA CAG TTG CCT AAA ATC CAA GCG CAA 1737 Leu Gly Leu Ala Gly Leu Ser Gin Gin Leu Pro Lys He Gin Ala Gin 385 390 395 400 ATC CGT CCG ATC GGT CCT AGC CAG ACA ACG ACC ATT GGA CAG ACG CAG 1785 He Arg Pro He Gly Pro Ser Gin Thr Thr Thr He Gly Gin Thr Gin 405 410 415 GTG CGT ATG ATA ACG CCG AAT GCC TTG GGC ACG CCG CGA CCC ACC ATT 1833 Val Arg Met He Thr Pro Asn Ala Leu Gly Thr Pro Arg Pro Thr He 420 425 430 49 GGC CAC ACC ACG ATA TCG AAG CAG CCA CCG AAT ATT CGG TTG CCT ACG 1881 Gly His Thr Thr He Ser Lys Gin Pro Pro Asn He Arg Leu Pro Thr 435 440 445 GCC CCG CGT CTC GTC AAC ACT GGA GGA ATT CGC ACC CAG ATA CCC TCG 1929 Ala Pro Arg Leu Val Asn Thr Gly Gly He Arg Thr Gin He Pro Ser 450 455 460 TTG CAG GTG CCT GGT CAG GCG AAC ATT GTG CAA ATA CGT GGA CCG CAG 1977 Leu Gin Val Pro Gly Gin Ala Asn He Val Gin He Arg Gly Pro Gin 465 470 475 480 CAT GCT CAG CTG CAG CGT ACT GGA TCG GTC CAG ATC CGG GCC ACC ACT 2025 His Ala Gin Leu Gin Arg Thr Gly Ser Val Gin He Arg Ala Thr Thr 485 490 495 CGT CCG CCA AAC AGT GTG CCC ACC GCG AAC AAA CTC ACT GCC GTC AAG 2073 Arg Pro Pro Asn Ser Val Pro Thr Ala Asn Lys Leu Thr Ala Val Lys 500 505 510 GTG GGA CAG ACG CAA ATC AAA GCG ATT ACG CCC AGC CTG CAT CCA CCC 2121 Val Gly Gin Thr Gin He Lys Ala He Thr Pro Ser Leu His Pro Pro 515 520 525 TCG CTG GCG GCA ATC TCA GGT GGA CCA CCG CCG ACA CCC ACG CTG TCT 2169 Ser Leu Ala Ala He Ser Gly Gly Pro Pro Pro Thr Pro Thr Leu Ser 50 530 535 540 GTT TTG TCT ACG TTG AAC TCC GCC TCG ACC ACA ACG CTG CCC ATA CCA 2217 Val Leu Ser Thr Leu Asn Ser Ala Ser Thr Thr Thr Leu Pro He Pro 545 550 555 560 TCG TTA CCC ACG GTC CAC CTT CCC CCC GAA GCT CTT CGA GCC CGT GAG 2265 Ser Leu Pro Thr Val His Leu Pro Pro Glu Ala Leu Arg Ala Arg Glu 565 570 575 CAG ATG CAA AAT TCG CTG AAC CAC AAC AGC AAT CAC TTC GAT GCA AAA 2313 Gin Met Gin Asn Ser Leu Asn His Asn Ser Asn His Phe Asp Ala Lys 580 585 590 CTG GTG GAG ATC AAG GCG CCG TCG CTG CAT CCG CCG CAC ATG GAG CGG 2361 Leu Val Glu He Lys Ala Pro Ser Leu His Pro Pro His Met Glu Arg 595 600 605 ATC AAC GCA TCT CTC ACA CCG ATT GGA GCC AAG ACG ATG GCA AGG CCG 2409 He Asn Ala Ser Leu Thr Pro He Gly Ala Lys Thr Met Ala Arg Pro 610 615 620 CCG CCT GCG ATC AAC AAG GCG ATA GGG AAA AAG AAA CGC GAC GCC ATG 2457 Pro Pro Ala He Asn Lys Ala He Gly Lys Lys Lys Arg Asp Ala Met 625 630 635 640 GAA ATG GAC GCC AAA TTG AAC ACA TCG AGC GGA GGA GCG GCG TCC GCT 2505 51 Glu Met Asp Ala Lys Leu Asn Thr Ser Ser Gly Gly Ala Ala Ser Ala 645 650 655 GCG AAC TCG TTT TTC CAG CAG AGC TCC ATG TCC TCG ATG TAC GGT GAC 2553 Ala Asn Ser Phe Phe Gin Gin Ser Ser Met Ser Ser Met Tyr Gly Asp 660 665 670 GAT GAT ATC AAC GAT GTT GCC GCC ATG GGA GGT GTT AAC TTG GCG GAG 2601 Asp Asp He Asn Asp Val Ala Ala Met Gly Gly Val Asn Leu Ala Glu 675 680 685 GAG TCG CAG CGA ATT CTC GGC TGT ACC GAA AAC ATC GGC ACG CAG ATT 2649 Glu Ser Gin Arg He Leu Gly Cys Thr Glu Asn He Gly Thr Gin He 690 695 700 CGA TCC TGC AAA GAT GAG GTT TTT CTT AAT CTC CCC TCG CTG CAA GCT 2697 Arg Ser Cys Lys Asp Glu Val Phe Leu Asn Leu Pro Ser Leu Gin Ala 705 710 715 720 AGA ATA CGG GCA ATT ACT TCG GAG GCG GGA CTG GAT GAG CCG TCG CAG 2745 Arg He Arg Ala He Thr Ser Glu Ala Gly Leu Asp Glu Pro Ser Gin 725 730 735 GAT GTG GCC GTT CTG ATA TCG CAC GCC TGT CAG GAG CGC CTG AAG AAC 2793 Asp Val Ala Val Leu He Ser His Ala Cys Gin Glu Arg Leu Lys Asn 740 745 750 52 ATC GTT GAG AAG TTG GCT GTG ATA GCG GAG CAC CGC ATT GAT GTC ATC 2841 He Val Glu Lys Leu Ala Val He Ala Glu His Arg He Asp Val He 755 760 765 AAG TTG GAT CCA CGC TAT GAG CCC GCC AAG GAT GTG CGC GGT CAG ATC 2889 Lys Leu Asp Pro Arg Tyr Glu Pro Ala Lys Asp Val Arg Gly Gin He 770 775 780 AAG TTT CTC GAG GAG CTG GAC AAG GCC GAG CAG AAG CGA CAC GAG GAA 2937 Lys Phe Leu Glu Glu Leu Asp Lys Ala Glu Gin Lys Arg His Glu Glu 785 790 795 800 CTG GAG CGT GAG ATG CTG CTG CGG GCA GCC AAG TCA CGG TCG AGG GTG 2985 Leu Glu Arg Glu Met Leu Leu Arg Ala Ala Lys Ser Arg Ser Arg Val 805 810 815 GAA GAT CCC GAG CAG GCC AAG ATG AAG GCG AGG GCC AAG GAG ATG CAA 3033 Glu Asp Pro Glu Gin Ala Lys Met Lys Ala Arg Ala Lys Glu Met Gin 820 825 830 CGC GCC GAA ATG GAG GAG TTG CGT CAA CGA GAT GCC AAT CTG ACG GCG 3081 Arg Ala Glu Met Glu Glu Leu Arg Gin Arg Asp Ala Asn Leu Thr Ala 835 840 845 CTG CAG GCG ATT GGA CCT CGG AAA AAG CTG AAG CTG GAC GGC GAA ACA 3129 Leu Gin Ala He Gly Pro Arg Lys Lys Leu Lys Leu Asp Gly Glu Thr 53 850 855 860 GTC AGT TCG GGA GCG GGT TCA AGT GGC GGC GGA GTG CTA AGC AGC TCG 3177 Val Ser Ser Gly Ala Gly Ser Ser Gly Gly Gly Val Leu Ser Ser Ser 865 870 875 880 GGA TCT GCG CCG ACG ACG TTA CGG CCT CGC ATA AAA CGT GTG AAC CTG 3225 Gly Ser Ala Pro Thr Thr Leu Arg Pro Arg He Lys Arg Val Asn Leu 885 890 895 CGC GAC ATG CTC TTC TAC ATG GAG CAA GAG CGG GAG TTC TGT CGC AGT 3273 Arg Asp Met Leu Phe Tyr Met Glu Gin Glu Arg Glu Phe Cys Arg Ser 900 905 910 TCC ATG CTG TTC AAG ACA TAC CTC AAG TGATCGCTGC TGTTGCCCAT 3320 Ser Met Leu Phe Lys Thr Tyr Leu Lys 915 920 CAATCGCACC GTCTTCTCCT CGCCGATCCT CCTACTCCGT GGACTGTCGT GTTGTTGTTT 3380 TATACAGCTT TACGATTTCA TCCACTTGCA ATATATTTTA GCCTCAACTT TAAATGCGTC 3440 GCGTGTCCCC TGTTGTTGTT TCTTTTTAGT TAGGCGGCTC TATTTAATTT CTATTTTTAC 3500 ATTTATTTAC ATAAATCCTA AATTCTAATC GTATTTGATT TTAAGCCTAA TTTAAAGCTC 3560 GTTTATTTTT CCAATAAATT CTCTGTAAAA CTTAAACCAA ACCAATCCAA AAACAAAACA 3620 54 AAACCAGAGT AAACGAAGAG AATAAAATAA TAGAGAGGAA AGTAAAAGAA GGTAAAAGAG 3680 AGCGCGCAGT CAGCGGTCGT TTGATTTGTA ATTTGTAACA TAATAATGTT TGCATCAACT 3740 GCATTGACGG CCTTATCTAA ACGATATAAA CATAATTATT AATATTTAAT TATTTAGCTT 3800 AGTTTGTTAA ACGAAAACGA ACCATAATTC CTAGATTTTA AGTAAAAAGC AAGGGCGCGT 3860 GAAGAGAAAT CGAAACCGAA TTACAGATAA AGGTTTTTAA AACCAACTAG ATCGAAACAA 3920 GTTCAGCAAC AGCAAAACAA AAGAACACAT CAAAAAAAGA ACCGAAAAAT ATCCATTTAA 3980 ACATCCATTG AATTAGGTTT AGTTGTTTAA AAAAGATGTA ATTTTTAATT ACCCATAATG 4040 TATAAACGGA AATCAATCGT TAGGCAAGAC CACAACAAAC CCAACAAATT GTAAATACAT 4100 TCTAGGCTAC GGTTTTTCTA ATAGATAACT AGGTAAAAAC GCAAACGTAA TTAACAAATT 4160 ATCGATGGCA AGGAGCGATG CGAGCGCAGA CAACTTGGCA CACCGAAAAA ATATGTTTTT 4220 ATTAGTGGCG CTCGTTCATC CATTAAGAAT GGCGATTCAT TAGGCTCCAT AGATCCATAA 4280 ATCCCCTAAT CCAATCTGAA CTACACACAA AATAGACAAA TTTTATACAA TTAGCTCGAT 4340 AAATCTTGTA AAATAGAGTC CCGTAAAAAA TTATAACAAA TAAATTGACA ACAATTGATG 4400 TAATTCAGTA AACCTAAGCA AAAAGTGAAA CCATTCTAAG CAAATTCTTT GTGTGTAAAA 55 4460 ATTAATATGA TAAACAAAAT GCAGATGCAA CCGTAAACAG CGCATAGTTT GGTAGGCATA 4520 TAACTGAATA TATATATATT ATTATTATTA TGTTTTAACA TTAAGCAAAA AAATAAAAGA 4580 AAAAATTGAG AAAACTTCAA AAAAAAAAAA AAAAA 4615 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 921 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Met Asn Thr Ser Gin Thr Ala Ala Gly Asn Arg He Thr Phe Thr Ser 1 5 10 15 Gin Pro Leu Pro Asn Gly Thr He Ser He Ala Gly Asn Pro Gly Ala 20 25 30 Val He Ser Thr Ala Gin Leu Pro Asn Thr Thr Thr He Lys Thr He 35 40 45 Gin Ala Gly He Gly Gly Gin His Gin Gly Leu Gin Gin Val His His 50 55 60 Val Gin Gin Gin Gin Gin Ser Gin Gin Gin Gin Gin Gin Gin Gin Gin 65 70 75 80 Thr Gin Ser Ala Gly Gin Pro Leu Leu Asn Ser Met Leu Pro Ala Gly 56 85 90 95 Val Val Val Gly Met Arg Gin Gin Ala Pro Ser Gin Gin Gin Gin Lys 100 105 110 Asn Val Pro Thr Asn Pro Leu Ser Arg Val Val He Asn Ser His Met 115 120 125 Ala Gly Val Arg Pro Gin Ser Pro Ser He Thr Leu Ser Thr Leu Asn 130 135 140 Thr Gly Gin Thr Pro Ala Leu Leu Val Lys Thr Asp Asn Gly Phe Gin 145 150 155 160 Leu Leu Arg Val Gly Thr Thr Thr Gly Pro Pro Thr Val Thr Gin Thr 165 170 175 He Thr Asn Thr Ser Asn Asn Ser Asn Thr Thr Ser Thr Thr Asn His 180 185 190 Pro Thr Thr Thr Gin He Arg Leu Gin Thr Val Pro Ala Ala Ala Ser 195 200 205 Met Thr Asn Thr Thr Ala Thr Ser Asn He He Val Asn Ser Val Ala 210 215 220 Ser Ser Gly Tyr Ala Asn Ser Ser Gin Pro Pro His Leu Thr Gin Leu 225 230 235 240 Asn Ala Gin Ala Pro Gin Leu Pro Gin He Thr Gin He Gin Thr He 245 250 255 57 Pro Ala Gin Gin Ser Gin Gin Gin Gin Val Asn Asn Val Ser Ser Ala 260 265 270 Gly Gly Thr Ala Thr Ala Val Ser Ser Thr Thr Ala Ala Thr Thr Thr 275 280 285 Gin Gin Gly Asn Thr Lys Glu Lys Cys Arg Lys Phe Leu Ala Asn Leu 290 295 300 He Glu Leu Ser Thr Arg Glu Pro Lys Pro Val Glu Lys Asn Val Arg 305 310 315 320 Thr Leu He Gin Glu Leu Val Asn Ala Asn Val Glu Pro Glu Glu Phe 325 330 335 Cys Asp Arg Leu Glu Arg Leu Leu Asn Ala Ser Pro Gin Pro Cys Leu 340 345 350 He Gly Phe Leu Lys Lys Ser Leu Pro Leu Leu Arg Gin Ala Leu Tyr 355 360 365 Thr Lys Glu Leu Val He Glu Gly He Lys Pro Pro Pro Gin His Val 370 375 380 Leu Gly Leu Ala Gly Leu Ser Gin Gin Leu Pro Lys He Gin Ala Gin 385 390 395 400 He Arg Pro He Gly Pro Ser Gin Thr Thr Thr He Gly Gin Thr Gin 405 410 415 Val Arg Met He Thr Pro Asn Ala Leu Gly Thr Pro Arg Pro Thr He 420 425 430 58 Gly His Thr Thr He Ser Lys Gin Pro Pro Asn He Arg Leu Pro Thr 435 440 445 Ala Pro Arg Leu Val Asn Thr Gly Gly He Arg Thr Gin He Pro Ser 450 455 460 Leu Gin Val Pro Gly Gin Ala Asn He Val Gin He Arg Gly Pro Gin 465 470 475 480 His Ala Gin Leu Gin Arg Thr Gly Ser Val Gin He Arg Ala Thr Thr 485 490 495 Arg Pro Pro Asn Ser Val Pro Thr Ala Asn Lys Leu Thr Ala Val Lys 500 505 510 Val Gly Gin Thr Gin He Lys Ala He Thr Pro Ser Leu His Pro Pro 515 520 525 Ser Leu Ala Ala He Ser Gly Gly Pro Pro Pro Thr Pro Thr Leu Ser 530 535 540 Val Leu Ser Thr Leu Asn Ser Ala Ser Thr Thr Thr Leu Pro He Pro 545 550 555 560 Ser Leu Pro Thr Val His Leu Pro Pro Glu Ala Leu Arg Ala Arg Glu 565 570 575 Gin Met Gin Asn Ser Leu Asn His Asn Ser Asn His Phe Asp Ala Lys 580 585 590 Leu Val Glu He Lys Ala Pro Ser Leu His Pro Pro His Met Glu Arg 595 600 605 59 He Asn Ala Ser Leu Thr Pro He Gly Ala Lys Thr Met Ala Arg Pro 610 615 620 Pro Pro Ala He Asn Lys Ala He Gly Lys Lys Lys Arg Asp Ala Met 625 630 635 640 Glu Met Asp Ala Lys Leu Asn Thr Ser Ser Gly Gly Ala Ala Ser Ala 645 650 655 Ala Asn Ser Phe Phe Gin Gin Ser Ser Met Ser Ser Met Tyr Gly Asp 660 665 670 Asp Asp He Asn Asp Val Ala Ala Met Gly Gly Val Asn Leu Ala Glu 675 680 685 Glu Ser Gin Arg He Leu Gly Cys Thr Glu Asn He Gly Thr Gin He 690 695 700 Arg Ser Cys Lys Asp Glu Val Phe Leu Asn Leu Pro Ser Leu Gin Ala 705 710 715 720 Arg He Arg Ala He Thr Ser Glu Ala Gly Leu Asp Glu Pro Ser Gin 725 730 735 Asp Val Ala Val Leu He Ser His Ala Cys Gin Glu Arg Leu Lys Asn 740 745 750 He Val Glu Lys Leu Ala Val He Ala Glu His Arg He Asp Val He 755 760 765 Lys Leu Asp Pro Arg Tyr Glu Pro Ala Lys Asp Val Arg Gly Gin He 770 775 780 60 Lys Phe Leu Glu Glu Leu Asp Lys Ala Glu Gin Lys Arg His Glu Glu 785 790 795 800 Leu Glu Arg Glu Met Leu Leu Arg Ala Ala Lys Ser Arg Ser Arg Val 805 810 815 Glu Asp Pro Glu Gin Ala Lys Met Lys Ala Arg Ala Lys Glu Met Gin 820 825 830 Arg Ala Glu Met Glu Glu Leu Arg Gin Arg Asp Ala Asn Leu Thr Ala 835 840 845 Leu Gin Ala He Gly Pro Arg Lys Lys Leu Lys Leu Asp Gly Glu Thr 850 855 860 Val Ser Ser Gly Ala Gly Ser Ser Gly Gly Gly Val Leu Ser Ser Ser 865 870 875 880 Gly Ser Ala Pro Thr Thr Leu Arg Pro Arg He Lys Arg Val Asn Leu 885 890 895 Arg Asp Met Leu Phe Tyr Met Glu Gin Glu Arg Glu Phe Cys Arg Ser 900 905 910 Ser Met Leu Phe Lys Thr Tyr Leu Lys 915 920 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4164 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA 61 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3: TTCGCTGTAC GAGGTACCCG GTCCGAATTC CAAAAGGGCC AACAACTTCA CCCGTGACTT 60 TCTGCAGGTG TTTATTTACC GCCTGTTCTG GAAAAGTCGC GACAACCCGC CCCGCATTCG 120 AATGGACGAT ATAAAACAGG CTTTTCCCGC TCATTCCGAG AGCAGCATCC GCAAGCGTTT 180 AAAGCAGTGC GCTGACTTCA AGCGAACAGG CATGGACTCC AATTGGTGGG TTATAAAGCC 240 AGAGTTTCGC CTTCCATCCG AGGAGGAGAT CCGAGCCATG GTGTCACCTG AGCAGTGTTG 300 CGGTACTTCA GCATGATAGC GGCGGAACAA CGCTTAAAGG ATGCTGGGTA TGGAGAAAAG 360 TTTTTGTTCG CACCTCAGGA AGATGACGAC GAGGAGGCGC AGTGAAAGCT TGACGACGAA 420 GTAAAGGTGG CTCCTTGGAA CACGACTCGC GCATATATCC AAGCCATGCG GGGAAAGTGT 480 TTACTCCAGT TGAGTGGTCC AGCCGATCCA ACGGGATGTG GAGAGGGATT TTCATATGTT 540 CGAGTGCCAA ACAAGCCCAC GCAAACCAAG GAGGAGCAAG AGTCGCAGCC TAAACGTTCG 600 GTCACAGGAA CAGATGCAGA TTTGCGTCGT CTGCCACTCC AGCGTGCAAA AGAGCTGTTG 660 CGGCAGTTCA AGGTGCCCGA GGAGGAGATC AAAAAGCTTT CCCGCTGGGA GGTCATTGAC 720 GTGGTGCGCA CCCTGTCCAC AGAAAAGGCC AAGGCCGGTG AAGAGGGAAT GGATAAGTTT 780 62 TCTCGTGGCA ACCGGTTCTC CATTGCAGAG CATCAGGAGC GTTATAAGGA AGAGTGCCAG 840 CGCATATTCG ATCTGCAAAA CAGAGTGCTG GCCAGCTCTG AGGTGCTGTC CACAGATGAG 900 GCAGAGTCCT CGGCCTCTGA GGAATCTGAT CTCGAAGAAC TTGGCAAGAA TCTTGAGAAC 960 ATGCTGTCAA ACAAGAAAAC CTCGACGCAA TTGTCAAGGG AACGTGAAGA GCTGGAGCGT 1020 CAGGAGTTGC TTCGCCAGCT TGACGAAGAA CACGGCGGAC CAAGTGGTAG TGGAGGAGCC 1080 AAGGGAGCCA AAGGAAAGGA TGATCCGGGA CAGCAAATGC TGGCAACCAA CAACCAGGGC 1140 AGGATCCTTC GCATTACGCG TACCTTTAGA GGTAACGATG GCAAGGAATA TACTCGCGTG 1200 GAGACTGTGC GGCGGCAACC AGTTATCGAC GCCTACATCA AGATTCGCAC CACTAAGGAC 1260 GAGCAGTTCA TCAAGCAGTT CGCAACGCTA GATGAGCAGC AGAAGGAGGA GATGAAGCGC 1320 GAAAAGAGAC GCATTCAGGA GCAGCTACGT CGCATCAAGC GCAACCAGGA GCGCGAACGC 1380 CTGGCGCAGC TGGCCCAGAA CCAGAAGCTT CAGCCAGGTG GCATGCCCAC TTCCTTGGGT 1440 GATCCTAAGA GCTCGGGCGG TCATTCGCAC AAGGAGCGGG ATAGCGGCTA CAAGGAGGTC 1500 AGCCCTTCGC GCAAGAAGTT CAAGCTTAAG CCAGACCTAA AGCTGAAGTG CGGCGCCTGT 1560 GGACAGGTTG GTCACATGCG CACAAACAAA GCCTGTCCCT TGTATTCTGG CATGCAAAGC 63 1620 AGTCTGTCCC AGTCGAACCC ATCTCTGGCT GACGATTTTG ACGAACAGAG CGAAAAGGAG 1680 ATGACAATGG ATGACGATGA TCTTGTGAAT GTCGATGGCA CCAAAGTAAC GCTCAGCAGT 1740 AAGATTCTCA AGCGTCATGG TGGTGATGAT GGCAAGCGTC GCAGCGGATC TAGCTCTGGT 1800 TTCACCTTGA AGGTTCCCCG AGATGCGATG GGCAAGAAGA AACGCAGAGT GGGTGGCGAT 1860 CTTCATTGTG ACTATCTGCA GCGACACAAT AAAACGGCCA ATCGCAGGCG CACGGACCCC 1920 GTTGTGGTAC TGTCCTCTAT CCTGGAGATT ATCCATAATG AGCTGCGATC TATGCCAGAT 1980 GTATCGCCAT TCCTGTTCCC GGTAAGCGCA AAAAAGGTTC CCGACTACTA CCGCGTGGTG 2040 ACCAAGCCCA TGGATCTGCA AACGATGAGG GAGTATATCG CCAAAGGCTA ACACGAGTCG 2100 CGAGATGTTC CTCGAGGATC TCAAGCAGAT TGTGGACAAC TCGCTGATCT ACAATGGACC 2160 GCAGAGTGCA TACACCTTGG CTGCCCAACG CATGTTCAGC AGTTGTTTTG AATTGCTCGC 2220 AGAGGCGAAG ACAAACTGAT GCGCCTCGAG AAGGCAATTA ACCCGCTGCT GGACGACGAT 2280 GACCAAGTGG CACTCTCCTT TATCTTTGAC AAGCTGCACT CGCAGATTAA GCAATTACCA 2340 GAGAGCTGGC CTTTCCTTAA GCCTGTCAAC AAGAAACAGG TTAAGGACTA CTACACGGTT 2400 64 ATCAAGCGAC CCATGGACCT CGAAACTATC GGCAAAAACA TTGAAGCTCA TCGCTATCAC 2460 AGTCGTGCCG AGTATCTGGC TGATATCGAG TTGATCGCCA CCAACTGTGA GCAGTACAAC 2520 GGCAGTGACA CCCGCTACAC CAAGTTCTCA AAGAAGATAC TTGAGTATGC CCAAACCCAG 2580 TTAATTGAGT TTTCGGAGCA CTGCGGCCAG TTGGAAAATA ACATAGCTAA GACGCAGGAG 2640 CGTGCTAGGG AAAATGCACC AGAGTTTGAT GAAGCCTGGG GCAATGATGA TTACAACTTT 2700 GACCGTGGCA GTAGGGCCAG TTCACCCGGA GATGACTACA TCGACGTCGA GGGTCATGGG 2760 GGGCATGCCT CCTCATCGAA CTCTATCCAT CGCAGCATGG GCGCCGAGGC CGGTTCGTCA 2820 CATACGGCGC CGGCGGTGCG AAAACCAGCT CCTCCTGGTC CTGGTGAGGT GAAGCGCGGA 2880 AGGGGTAGGC CCCGCAAGCA GCGCGACCCC GTGGAGGAGG TCAAATCCCA GAATCCGGTT 2940 AAGCGTGGTC GGGGGCGTCC GAGGAAGGAC AGCCTTGCCT CAAACATGAG TCACACGCAA 3000 GCTTACTTCC TGGATGAAGA TCTCCAATGC TCCACAGATG ACGAGGACGA CGACGAGGAG 3060 GAGGACTTCC AGGAGGTCTC CGAAGACGAG AACAATGCGG CGAGCATTTT AGATCAGGGC 3120 GAACGTATCA ATGCGCCTGC CGATGCCATG GATGGCATGT TTGACCCCAA GAACATCAAG 3180 ACAGAGATTG ACCTAGAGGC TCACCAGATG GCAGAGGAGC CGATCGGCGA GGATGACAGC 65 3240 CAGCAGGTGG CCGAAGCAAT GGTGCAGTTG AGTGGCGTGG GCGGCTACTA TGCTCAACAG 3300 CAGCAAGATG AATCCATGGA TGTGGACCCC AACTACGATC CCTCAGATTT CCTCGCCATG 3360 CACAAGCAGC GCCAGAGCCT CGGCGAGCCC AGCAGCTTGC AGGGTGCTTT CACCAACTTC 3420 CTATCGCACG AGCAGGATGA TAATGGGCCT TACAATCCCG CCGAAGCCAG CACAAGTGCC 3480 GCTTCCGGTG CAGACTTAGG AATGGACGCT TCAATGGCCA TGCAAATGGC GCCGGAAATG 3540 CCTGTCAATA CCATGAACAA CGGAATGGGC ATCGATGATG ATCTGGATAT TTCGGAGAGT 3600 GACGAGGAAG ACGATGGTTC TCGAGTGCGT ATCAAAAAGG AGGTCTTCGA CGACGGGGAT 3660 TACGCCTTGC AGCACCAGCA GATGGGACAG GCAGCATCGC AGTCGCAGAT ATACATGGGG 3720 ATTCGTCCAA CGAGCCCACG ACTCTCGACT ACCAGCAACC ACCGCAACTG GACTTCCAAC 3780 AAGTGCAGGA AATGGAGCAG TTGCAGCACC AAGTGATGCC ACCAATGCAA TCAGAGCAAC ACAGACGCCG CAGGAGACAA TGATTATGCC TGGACTTTTT AATAATTGTT AGTTGTTAGA AAATAAAACG TCGATTTAAT AATAGGATTG AGCTTCGCTG 3960 TGAAACAATT TTATACACTT TTTACAATGC ATTGTTTTAA CGGATTTTGA AATACTACAA 4020 6 6 TATGTTCTCT GAAAAAATAT TTCCTTTTCA TGCCAATATG TTTTTAATTT TACACTTTAC 4080 AATTTATGAA ATCTAATTCA AAATATGTTT TTAAAATATA ATTTTCATAA CTTTAAATAA 4140 TGCCTAGAAA AAAAAAAAAA AAAA 4164 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2359 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 49..2160 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: GATAACAAAA TAGTACACAA GTTCCATATA TTTCAATTTT CCGCGAAA ATG AGC CTG 57 Met Ser Leu GAA GTG AGC AAT ATC AAC GGG GGA AAC GGT ACT CAA TTG TCC CAC GAC 105 Glu Val Ser Asn He Asn Gly Gly Asn Gly Thr Gin Leu Ser His Asp 5 10 15 AAG CGT GAG CTG CTA TGC CTG CTG AAA CTC ATC AAA AAG TAC CAG CTG 153 Lys Arg Glu Leu Leu Cys Leu Leu Lys Leu He Lys Lys Tyr Gin Leu 20 25 30 35 67 AAG AGC ACT GAG GAG CTG CTC TGC CAA GAG GCG AAT GTG AGC AGT GTG 201 Lys Ser Thr Glu Glu Leu Leu Cys Gin Glu Ala Asn Val Ser Ser Val 40 45 50 GAA TTG TCG GAA ATC AGC GAA AGT GAT GTT CAG CAG GTG CTG GGC GCA 249 Glu Leu Ser Glu He Ser Glu Ser Asp Val Gin Gin Val Leu Gly Ala 55 60 65 GTT TTG GGA GCT GGC GAT GCC AAC CGG GAG CGG AAA CAT GTC CAA TCT 297 Val Leu Gly Ala Gly Asp Ala Asn Arg Glu Arg Lys His Val Gin Ser 70 75 80 CCG GCG CAG GGT CAT AAA CAG TCC GCG GTG ACG GAG GCC AAT GCT GCA 345 Pro Ala Gin Gly His Lys Gin Ser Ala Val Thr Glu Ala Asn Ala Ala 85 90 95 GAG GAA CTG GCC AAG TTC ATC GAC GAC GAC AGC TTT GAT GCT CAG CAC 393 Glu Glu Leu Ala Lys Phe He Asp Asp Asp Ser Phe Asp Ala Gin His 100 105 110 115 TAT GAG CAG GCA TAC AAG GAG CTG CGC ACT TTC GTT GAG GAC TCC CTG 441 Tyr Glu Gin Ala Tyr Lys Glu Leu Arg Thr Phe Val Glu Asp Ser Leu 120 125 130 GAC ATA TAC AAG CAT GAG CTG TCC ATG GTT CTG TAC CCA ATT CTG GTG 489 Asp He Tyr Lys His Glu Leu Ser Met Val Leu Tyr Pro He Leu Val 68 135 140 145 CAG ATC TAC TTC AAG ATC CTC GCC AGT GGA CTA AGG GAG AAG GCC AAA 537 Gin He Tyr Phe Lys He Leu Ala Ser Gly Leu Arg Glu Lys Ala Lys 150 155 160 GAA TTC ATT GAG AAG TAC AAA TGC GAT CTC GAC GGC TAC TAC ATA GAG 585 Glu Phe He Glu Lys Tyr Lys Cys Asp Leu Asp Gly Tyr Tyr He Glu 165 170 175 GGT CTT TTC AAC CTT CTT TTG CTG TCT AAG CCC GAG GAG CTG CTG GAG 633 Gly Leu Phe Asn Leu Leu Leu Leu Ser Lys Pro Glu Glu Leu Leu Glu 180 185 190 195 AAT GAC CTC GTA GTA GCC ATG GAG CAG GAT AAG TTT GTC ATT CGC ATG 681 Asn Asp Leu Val Val Ala Met Glu Gin Asp Lys Phe Val He Arg Met 200 205 210 TCC AGG GAC TCG CAC TCT CTG TTC AAG CGA CAC ATT CAG GAT CGC CGG 729 Ser Arg Asp Ser His Ser Leu Phe Lys Arg His He Gin Asp Arg Arg 215 220 225 CAG GAA GTG GTG GCA GAT ATT GTT TCC AAG TAC TTG CAT TTC GAC ACA 777 Gin Glu Val Val Ala Asp He Val Ser Lys Tyr Leu His Phe Asp Thr 230 235 240 TAC GAG GGC ATG GCG CGC AAC AAG CTG CAG TGC GTC GCC ACC GCG GGC 825 69 Tyr Glu Gly Met Ala Arg Asn Lys Leu Gin Cys Val Ala Thr Ala Gly 245 250 255 TCG CAC CTC GGA GAG GCC AAG CGA CAG GAC AAC AAA ATG CGG GTG TAC 873 Ser His Leu Gly Glu Ala Lys Arg Gin Asp Asn Lys Met Arg Val Tyr 260 265 270 275 TAC GGA CTG CTC AAG GAG GTG GAC TTT CAG ACT CTG ACC ACT CCA GCG 921 Tyr Gly Leu Leu Lys Glu Val Asp Phe Gin Thr Leu Thr Thr Pro Ala 280 285 290 CCG GCA CCA GAG GAG GAG GAC GAT GAT CCG GAT GCC CCG GAT CGT CCG 969 Pro Ala Pro Glu Glu Glu Asp Asp Asp Pro Asp Ala Pro Asp Arg Pro 295 300 305 AAA AAG AAA AAG CCA AAA AAG GAT CCC CTG CTG TCG AAA AAG TCC AAG 1017 Lys Lys Lys Lys Pro Lys Lys Asp Pro Leu Leu Ser Lys Lys Ser Lys 310 315 320 TCG GAT CCG AAT GCT CCA TCC ATC GAC AGA ATT CCC CTG CCG GAA CTG 1065 Ser Asp Pro Asn Ala Pro Ser He Asp Arg He Pro Leu Pro Glu Leu 325 330 335 AAG GAT TCG GAC AAG TTG CTA AAG CTT AAG GCT CTC AGG GAA GCC AGC 1113 Lys Asp Ser Asp Lys Leu Leu Lys Leu Lys Ala Leu Arg Glu Ala Ser 340 345 350 355 70 AAG CGT TTA GCC CTC AGC AAG GAT CAA CTG CCC TCT GCC GTC TTC TAC 1161 Lys Arg Leu Ala Leu Ser Lys Asp Gin Leu Pro Ser Ala Val Phe Tyr 360 365 370 ACG GTG CTT AAT TCC CAT CAG GGC GTA ACC TGT GCC GAG ATT TCA GAC 1209 Thr Val Leu Asn Ser His Gin Gly Val Thr Cys Ala Glu He Ser Asp 375 380 385 GAT TCC ACG ATG TTG GCC TGT GGA TTT GGC GAT TCT AGC GTG AGG ATT 1257 Asp Ser Thr Met Leu Ala Cys Gly Phe Gly Asp Ser Ser Val Arg He 390 395 400 TGG TCA TTG ACG CCC GCG AAG CTG CGT ACG CTG AAG GAT GCA GAT TCC 1305 Trp Ser Leu Thr Pro Ala Lys Leu Arg Thr Leu Lys Asp Ala Asp Ser 405 410 415 CTT CGC GAA CTG GAC AAG GAA TCG GCG GAT ATC AAT GTG CGT ATG CTG 1353 Leu Arg Glu Leu Asp Lys Glu Ser Ala Asp He Asn Val Arg Met Leu 420 425 430 435 GAT GAC CGA AGT GGT GAG GTA ACC AGG AGC TTA ATG GGT CAC ACC GGA 1401 Asp Asp Arg Ser Gly Glu Val Thr Arg Ser Leu Met Gly His Thr Gly 440 445 450 CCC GTA TAC CGC TGT GCC TTT GCC CCC GAG ATG AAC CTG TTG CTC TCA 1449 Pro Val Tyr Arg Cys Ala Phe Ala Pro Glu Met Asn Leu Leu Leu Ser 71 455 460 465 TGT TCC GAG GAC AGC ACC ATA AGG CTG TGG TCT CTG CTC ACC TGG TCC 1497 Cys Ser Glu Asp Ser Thr He Arg Leu Trp Ser Leu Leu Thr Trp Ser 470 475 480 TGC GTA GTC ACC TAC CGC GGG CAC GTT TAC CCG GTG TGG GAT GTT CGC 1545 Cys Val Val Thr Tyr Arg Gly His Val Tyr Pro Val Trp Asp Val Arg 485 490 495 TTT GCG CCG CAT GGC TAC TAT TTT GTT TCT TGT TCG TAC GAC AAA ACT 1593 Phe Ala Pro His Gly Tyr Tyr Phe Val Ser Cys Ser Tyr Asp Lys Thr 500 505 510 515 GCT CGT CTG TGG GCC ACG GAT TCC AAT CAA GCG TTG CGC GTA TTC GTG 1641 Ala Arg Leu Trp Ala Thr Asp Ser Asn Gin Ala Leu Arg Val Phe Val 520 525 530 GGT CAC TTG TCG GAC GTG GAT TGT GTA CAA TTT CAT CCC AAT TCC AAT 1689 Gly His Leu Ser Asp Val Asp Cys Val Gin Phe His Pro Asn Ser Asn 535 540 545 TAT GTG GCC ACC GGT TCT AGC GAT CGC ACG GTA CGC CTG TGG GAC AAC 1737 Tyr Val Ala Thr Gly Ser Ser Asp Arg Thr Val Arg Leu Trp Asp Asn 550 555 560 ATG ACC GGT CAG TCG GTA CGC CTG ATG ACG GGC CAC AAG GGA TCG GTG 1785 72 Met Thr Gly Gin Ser Val Arg Leu Met Thr Gly His Lys Gly Ser Val 565 570 575 AGT TCT CTG GCC TTC TCC GCC TGC GGC CGG TAT CTG GCC TCG GGT TCA 1833 Ser Ser Leu Ala Phe Ser Ala Cys Gly Arg Tyr Leu Ala Ser Gly Ser 580 585 590 595 GTA GAT CAC AAT ATC ATC ATC TGG GAT CTG TCG AAC GGA TCC CTG GTC 1881 Val Asp His Asn He He He Trp Asp Leu Ser Asn Gly Ser Leu Val 600 605 610 ACC ACC CTG TTG AGG CAC ACT AGC ACT GTG ACC ACG ATC ACC TTT AGT 1929 Thr Thr Leu Leu Arg His Thr Ser Thr Val Thr Thr He Thr Phe Ser 615 620 625 CGC GAT GGA ACA GTC CTG GCT GCA GCC GGC TTG GAT AAC AAT CTA ACT 1977 Arg Asp Gly Thr Val Leu Ala Ala Ala Gly Leu Asp Asn Asn Leu Thr 630 635 640 CTG TGG GAC TTT CAC AAG GTT ACC GAA GAC TAT ATC AGC AAT CAC ATC 2025 Leu Trp Asp Phe His Lys Val Thr Glu Asp Tyr He Ser Asn His He 645 650 655 ACT GTG TCG CAC CAT CAG GAT GAG AAC GAC GAG GAC GTC TAC CTC ATG 2073 Thr Val Ser His His Gin Asp Glu Asn Asp Glu Asp Val Tyr Leu Met 660 665 670 675 73 CGT ACT TTC CCC AGC AAG AAC TCG CCA TTT GTC AGC CTG CAC TTT ACG 2121 Arg Thr Phe Pro Ser Lys Asn Ser Pro Phe Val Ser Leu His Phe Thr 680 685 690 CGC CGA AAT CTC CTG ATG TGC GTG GGT CTA TTC AAG AGT TAGGAGCACA 2170 Arg Arg Asn Leu Leu Met Cys Val Gly Leu Phe Lys Ser 695 700 GATAAGCTTA TTTGGTATAC GTAATGTAGT GTTAAGGAAT GCTCGGAATG TTTAGGATTA 2230 ATGTTTTGTA TTTCGTTTGT GACCCATCCC CCCTGAAATG TCGATTAGTT GTTTAAGCAT 2290 AAAAGTGTAA AGTGCATATA TGCGCAAGTT ATCAATAAAT TTTAATTAAT ATAAAAGTCA 2350 AAAAAAAAA 2359 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 704 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: Met Ser Leu Glu Val Ser Asn He Asn Gly Gly Asn Gly Thr Gin Leu 1 5 10 15 Ser His Asp Lys Arg Glu Leu Leu Cys Leu Leu Lys Leu He Lys Lys 20 25 30 74 Tyr Gin Leu Lys Ser Thr Glu Glu Leu Leu Cys Gin Glu Ala Asn Val 35 40 45 Ser Ser Val Glu Leu Ser Glu He Ser Glu Ser Asp Val Gin Gin Val 50 55 60 Leu Gly Ala Val Leu Gly Ala Gly Asp Ala Asn Arg Glu Arg Lys His 65 70 75 80 Val Gin Ser Pro Ala Gin Gly His Lys Gin Ser Ala Val Thr Glu Ala 85 90 95 Asn Ala Ala Glu Glu Leu Ala Lys Phe He Asp Asp Asp Ser Phe Asp 100 105 110 Ala Gin His Tyr Glu Gin Ala Tyr Lys Glu Leu Arg Thr Phe Val Glu 115 120 125 Asp Ser Leu Asp He Tyr Lys His Glu Leu Ser Met Val Leu Tyr Pro 130 135 140 He Leu Val Gin He Tyr Phe Lys He Leu Ala Ser Gly Leu Arg Glu 145 150 155 160 Lys Ala Lys Glu Phe He Glu Lys Tyr Lys Cys Asp Leu Asp Gly Tyr 165 170 175 Tyr He Glu Gly Leu Phe Asn Leu Leu Leu Leu Ser Lys Pro Glu Glu 180 185 190 Leu Leu Glu Asn Asp Leu Val Val Ala Met Glu Gin Asp Lys Phe Val 195 200 205 75 lie Arg Met Ser Arg Asp Ser His Ser Leu Phe Lys Arg His lie Gin 210 215 220 Asp Arg Arg Gin Glu Val Val Ala Asp He Val Ser Lys Tyr Leu His 225 230 235 240 Phe Asp Thr Tyr Glu Gly Met Ala Arg Asn Lys Leu Gin Cys Val Ala 245 250 255 Thr Ala Gly Ser His Leu Gly Glu Ala Lys Arg Gin Asp Asn Lys Met 260 265 270 Arg Val Tyr Tyr Gly Leu Leu Lys Glu Val Asp Phe Gin Thr Leu Thr 275 280 285 Thr Pro Ala Pro Ala Pro Glu Glu Glu Asp Asp Asp Pro Asp Ala Pro 290 295 300 Asp Arg Pro Lys Lys Lys Lys Pro Lys Lys Asp Pro Leu Leu Ser Lys 305 310 315 320 Lys Ser Lys Ser Asp Pro Asn Ala Pro Ser He Asp Arg He Pro Leu 325 330 335 Pro Glu Leu Lys Asp Ser Asp Lys Leu Leu Lys Leu Lys Ala Leu Arg 340 345 350 Glu Ala Ser Lys Arg Leu Ala Leu Ser Lys Asp Gin Leu Pro Ser Ala 355 360 365 Val Phe Tyr Thr Val Leu Asn Ser His Gin Gly Val Thr Cys Ala Glu 370 375 380 76 He Ser Asp Asp Ser Thr Met Leu Ala Cys Gly Phe Gly Asp Ser Ser 385 390 395 400 Val Arg He Trp Ser Leu Thr Pro Ala Lys Leu Arg Thr Leu Lys Asp 405 410 415 Ala Asp Ser Leu Arg Glu Leu Asp Lys Glu Ser Ala Asp He Asn Val 420 425 430 Arg Met Leu Asp Asp Arg Ser Gly Glu Val Thr Arg Ser Leu Met Gly 435 440 445 His Thr Gly Pro Val Tyr Arg Cys Ala Phe Ala Pro Glu Met Asn Leu 450 455 460 Leu Leu Ser Cys Ser Glu Asp Ser Thr He Arg Leu Trp Ser Leu Leu 465 470 475 480 Thr Trp Ser Cys Val Val Thr Tyr Arg Gly His Val Tyr Pro Val Trp 485 490 495 Asp Val Arg Phe Ala Pro His Gly Tyr Tyr Phe Val Ser Cys Ser Tyr 500 505 510 Asp Lys Thr Ala Arg Leu Trp Ala Thr Asp Ser Asn Gin Ala Leu Arg 515 520 525 Val Phe Val Gly His Leu Ser Asp Val Asp Cys Val Gin Phe His Pro 530 535 540 Asn Ser Asn Tyr Val Ala Thr Gly Ser Ser Asp Arg Thr Val Arg Leu 545 550 555 560 77 Trp Asp Asn Met Thr Gly Gin Ser Val Arg Leu Met Thr Gly His Lys 565 570 575 Gly Ser Val Ser Ser Leu Ala Phe Ser Ala Cys Gly Arg Tyr Leu Ala 580 585 590 Ser Gly Ser Val Asp His Asn He He He Trp Asp Leu Ser Asn Gly 595 600 605 Ser Leu Val Thr Thr Leu Leu Arg His Thr Ser Thr Val Thr Thr He 610 615 620 Thr Phe Ser Arg Asp Gly Thr Val Leu Ala Ala Ala Gly Leu Asp Asn 625 630 635 640 Asn Leu Thr Leu Trp Asp Phe His Lys Val Thr Glu Asp Tyr He Ser 645 650 655 Asn His He Thr Val Ser His His Gin Asp Glu Asn Asp Glu Asp Val 660 665 670 Tyr Leu Met Arg Thr Phe Pro Ser Lys Asn Ser Pro Phe Val Ser Leu 675 680 685 His Phe Thr Arg Arg Asn Leu Leu Met Cys Val Gly Leu Phe Lys Ser 690 695 700 (2) INFORMATION FOR SEQ ID NO: 6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2018 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear 78 (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 70..1842 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: GGAATTCGAG TTGGCCAAAG TGGCGCAATC CGGTATCAAT TGTTCAAACC GAGCAGCCCC 60 TCCAGCAGC ATG CTG TAC GGC TCC AGC ATC TCG GCG GAG TCC ATG AAG 108 Met Leu Tyr Gly Ser Ser He Ser Ala Glu Ser Met Lys 1 5 10 GTG ATC GCG GAG AGC ATC GGA GTG GGC TCC CTG TCG GAT GAC GCC GCC 156 Val He Ala Glu Ser He Gly Val Gly Ser Leu Ser Asp Asp Ala Ala 15 20 25 AAG GAA CTA GCG GAG GAT GTG TCC ATC AAG CTG AAG AGG ATT GTA CAG 204 Lys Glu Leu Ala Glu Asp Val Ser He Lys Leu Lys Arg He Val Gin 30 35 40 45 GAT GCG GCC AAG TTC ATG AAC CAC GCC AAG CGG CAG AAG CTC TCA GTG 252 Asp Ala Ala Lys Phe Met Asn His Ala Lys Arg Gin Lys Leu Ser Val 50 55 60 CGG GAC ATC GAC ATG TCC CTT AAG GTG CGA AAT GTG GAG CCG CAG TAC 300 Arg Asp He Asp Met Ser Leu Lys Val Arg Asn Val Glu Pro Gin Tyr 65 70 75 79 GGT TTC GTA GCC AAG GAC TTC ATT CCA CTC CGC TTC GCA TCT GGC GGA 348 Gly Phe Val Ala Lys Asp Phe He Pro Leu Arg Phe Ala Ser Gly Gly 80 85 90 GGA CGG GAG CTG CAC TTC ACC GAG GAC AAG GAA ATC GAC CTA GGA GAA 396 Gly Arg Glu Leu His Phe Thr Glu Asp Lys Glu He Asp Leu Gly Glu 95 100 105 ATC ACA TCC ACC AAC TCT GTA AAA ATT CCC CTG GAT CTC ACC CTG CGC 444 He Thr Ser Thr Asn Ser Val Lys He Pro Leu Asp Leu Thr Leu Arg 110 115 120 125 TCC CAT TGG TTT GTT GTG GAG GGA GTG CAA CCC ACT GTG CCC GAA AAC 492 Ser His Trp Phe Val Val Glu Gly Val Gin Pro Thr Val Pro Glu Asn 130 135 140 CCC CCT CCG CTC TCG AAG GAT TCC CAG TTA CTG GAC TCG GTC AAT CCA 540 Pro Pro Pro Leu Ser Lys Asp Ser Gin Leu Leu Asp Ser Val Asn Pro 145 150 155 GTT ATT AAG ATG GAT CAA GGC CTA AAC AAA GAT GCG GCA GGC AAA CCC 588 Val He Lys Met Asp Gin Gly Leu Asn Lys Asp Ala Ala Gly Lys Pro 160 165 170 ACC ACC GGC AAG ATA CAC AAG CTG AAA AAC GTG GAG ACC ATT CAT GTC 636 Thr Thr Gly Lys He His Lys Leu Lys Asn Val Glu Thr He His Val 80 175 180 185 AAG CAA CTG GCC ACG CAC GAG TTG TCC GTG GAG CAG CAG TTG TAC TAC 684 Lys Gin Leu Ala Thr His Glu Leu Ser Val Glu Gin Gin Leu Tyr Tyr 190 195 200 205 AAG GAG ATC ACC GAG GCG TGC GTG GGA TCT GAT GAG CCG CGG CGC GGG 732 Lys Glu He Thr Glu Ala Cys Val Gly Ser Asp Glu Pro Arg Arg Gly 210 215 220 GAA GCG CTG CAG TCG CTG GGA TCC GAT CCT GGC CTG CAC GAA ATG CTT 780 Glu Ala Leu Gin Ser Leu Gly Ser Asp Pro Gly Leu His Glu Met Leu 225 230 235 CCC CGC ATG TGC ACC TTC ATT GCC GAG GGA GTT AAG GTC AAT GTG GTT 828 Pro Arg Met Cys Thr Phe He Ala Glu Gly Val Lys Val Asn Val Val 240 245 250 CAG AAC AAC TTG GCG TTG CTT ATT TAC CTC ATG CGC ATG GTT CGT GCG 876 Gin Asn Asn Leu Ala Leu Leu He Tyr Leu Met Arg Met Val Arg Ala 255 260 265 CTT CTG GAT AAT CCT TCG CTG TTT CTG GAG AAA TAC CTC CAC GAA CTG 924 Leu Leu Asp Asn Pro Ser Leu Phe Leu Glu Lys Tyr Leu His Glu Leu 270 275 280 285 ATA CCC TCG GTG ATG ACG TGC ATT GTG TCC AAA CAG CTG TGT ATG CGC 972 81 He Pro Ser Val Met Thr Cys He Val Ser Lys Gin Leu Cys Met Arg 290 295 300 CCC GAG CTG GAC AAT CAC TGG GCC CTG CGA GAC TTT GCC TCC CGA CTG 1020 Pro Glu Leu Asp Asn His Trp Ala Leu Arg Asp Phe Ala Ser Arg Leu 305 310 315 ATG GCT CAA ATC TGC AAG AAC TTC AAT ACC CTA ACC AAC AAT CTG CAA 1068 Met Ala Gin He Cys Lys Asn Phe Asn Thr Leu Thr Asn Asn Leu Gin 320 325 330 ACC CGT GTC ACC CGC ATC TTC AGC AAG GCC CTG CAG AAC GAC AAG ACC 1116 Thr Arg Val Thr Arg He Phe Ser Lys Ala Leu Gin Asn Asp Lys Thr 335 340 345 CAC CTG TCC TCG CTT TAC GGC TCT ATT GCG GGT CTC TCG GAG CTG GGG 1164 His Leu Ser Ser Leu Tyr Gly Ser He Ala Gly Leu Ser Glu Leu Gly 350 355 360 365 GGC GAA GTC ATA AAG GTT TTC ATC ATA CCC CGC CTT AAG TTC ATA TCG 1212 Gly Glu Val He Lys Val Phe He He Pro Arg Leu Lys Phe He Ser 370 375 380 GAG CGC ATT GAA CCT CAC CTG CTC GGC ACC TCC ATC AGC AAC ACT GAC 1260 Glu Arg He Glu Pro His Leu Leu Gly Thr Ser He Ser Asn Thr Asp 385 390 395 82 AAG ACA GCA GCA GGT CAC ATC CGC GCC ATG CTT CAG AAG TGC TGT CCC 1308 Lys Thr Ala Ala Gly His He Arg Ala Met Leu Gin Lys Cys Cys Pro 400 405 410 CCG ATT CTC AGG CAA ATG CTC AGC GCC AGA TAC AGC GGA GGA CTA CAA 1356 Pro He Leu Arg Gin Met Leu Ser Ala Arg Tyr Ser Gly Gly Leu Gin 415 420 425 GAA CGA CTT TGG CTT CCT GGG GCC GTC GCT GTG CCA GGC GTA GTC AAA 1404 Glu Arg Leu Trp Leu Pro Gly Ala Val Ala Val Pro Gly Val Val Lys 430 435 440 445 GTT CGA AAT GCG CCC GCC TCA AGC ATT GTA ACC CTG TCA TCC AAC ACT 1452 Val Arg Asn Ala Pro Ala Ser Ser He Val Thr Leu Ser Ser Asn Thr 450 455 460 ATC AAC ACG GCA CCC ATC ACG AGT GCA GCA CAA ACA GCA ACA ACC ATC 1500 He Asn Thr Ala Pro He Thr Ser Ala Ala Gin Thr Ala Thr Thr He 465 470 475 GGA CGA GTG TCC ATG CCC ACC ACA CAG AGA CAG GGA AGT CCC GGA GTC 1548 Gly Arg Val Ser Met Pro Thr Thr Gin Arg Gin Gly Ser Pro Gly Val 480 485 490 TCG TCC CTG CCG CAA ATA AGA GCC ATT CAG GCC AAC CAG CCG GCG CAA 1596 Ser Ser Leu Pro Gin He Arg Ala He Gin Ala Asn Gin Pro Ala Gin 83 495 500 505 AAG TTT GTG ATA GTC ACC CAG AAC TCG CCG CAG CAG GGC CAG GCG AAG 1644 Lys Phe Val He Val Thr Gin Asn Ser Pro Gin Gin Gly Gin Ala Lys 510 515 520 525 GTG GTG CGG CGT GGC AGC TCT CCG CAC AGC GTG GTC CTC TCC GCG GCC 1692 Val Val Arg Arg Gly Ser Ser Pro His Ser Val Val Leu Ser Ala Ala 530 535 540 TCC AAC GCT GCC AGT GCC TCC AAT TCG AAC TCA AGC TCG AGC GGC AGT 1740 Ser Asn Ala Ala Ser Ala Ser Asn Ser Asn Ser Ser Ser Ser Gly Ser 545 550 555 CTA CTA GCG GCT GCA CAG CGG AGC AGC GAG AAT GTG TGT GTT ATT GCC 1788 Leu Leu Ala Ala Ala Gin Arg Ser Ser Glu Asn Val Cys Val He Ala 560 565 570 GGT AGC GAA GCG CCA GCA GTT GAT GGT ATA ACA GTT CAA TCT TTC AGA 1836 Gly Ser Glu Ala Pro Ala Val Asp Gly He Thr Val Gin Ser Phe Arg 575 580 585 GCA TCC TAGACGCCAA CTCGCTGATC ATTGAGACGG AGATTGTGCG CGCACCGGCC 1892 Ala Ser 590 CGAGCTGGCG GATCTCTCGC ACCTGGAGTA GCCAGCTTAG TTCGTAGTCC ACATTTTGTC 1952 84 ATATTGTATG CAATAAAATA AAAAATGCGG GTTCCTACCC CAAAAAAATG TAAAAAAAAA 2012 AAAAAA 2018 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 591 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: Met Leu Tyr Gly Ser Ser He Ser Ala Glu Ser Met Lys Val He Ala 1 5 10 15 Glu Ser He Gly Val Gly Ser Leu Ser Asp Asp Ala Ala Lys Glu Leu 20 25 30 Ala Glu Asp Val Ser He Lys Leu Lys Arg He Val Gin Asp Ala Ala 35 40 45 Lys Phe Met Asn His Ala Lys Arg Gin Lys Leu Ser Val Arg Asp He 50 55 60 Asp Met Ser Leu Lys Val Arg Asn Val Glu Pro Gin Tyr Gly Phe Val 65 70 75 80 Ala Lys Asp Phe He Pro Leu Arg Phe Ala Ser Gly Gly Gly Arg Glu 85 90 95 Leu His Phe Thr Glu Asp Lys Glu He Asp Leu Gly Glu He Thr Ser 100 105 110 85 Thr Asn Ser Val Lys lie Pro Leu Asp Leu Thr Leu Arg Ser His Trp 115 120 125 Phe Val Val Glu Gly Val Gin Pro Thr Val Pro Glu Asn Pro Pro Pro 130 135 140 Leu Ser Lys Asp Ser Gin Leu Leu Asp Ser Val Asn Pro Val He Lys 145 150 155 160 Met Asp Gin Gly Leu Asn Lys Asp Ala Ala Gly Lys Pro Thr Thr Gly 165 170 175 Lys He His Lys Leu Lys Asn Val Glu Thr He His Val Lys Gin Leu 180 185 190 Ala Thr His Glu Leu Ser Val Glu Gin Gin Leu Tyr Tyr Lys Glu He 195 200 205 Thr Glu Ala Cys Val Gly Ser Asp Glu Pro Arg Arg Gly Glu Ala Leu 210 215 220 Gin Ser Leu Gly Ser Asp Pro Gly Leu His Glu Met Leu Pro Arg Met 225 230 235 240 Cys Thr Phe He Ala Glu Gly Val Lys Val Asn Val Val Gin Asn Asn 245 250 255 Leu Ala Leu Leu He Tyr Leu Met Arg Met Val Arg Ala Leu Leu Asp 260 265 270 Asn Pro Ser Leu Phe Leu Glu Lys Tyr Leu His Glu Leu He Pro Ser 275 280 285 86 Val Met Thr Cys He Val Ser Lys Gin Leu Cys Met Arg Pro Glu Leu 290 295 300 Asp Asn His Trp Ala Leu Arg Asp Phe Ala Ser Arg Leu Met Ala Gin 305 310 315 320 He Cys Lys Asn Phe Asn Thr Leu Thr Asn Asn Leu Gin Thr Arg Val 325 330 335 Thr Arg He Phe Ser Lys Ala Leu Gin Asn Asp Lys Thr His Leu Ser 340 345 350 Ser Leu Tyr Gly Ser He Ala Gly Leu Ser Glu Leu Gly Gly Glu Val 355 360 365 He Lys Val Phe He He Pro Arg Leu Lys Phe He Ser Glu Arg He 370 375 380 Glu Pro His Leu Leu Gly Thr Ser He Ser Asn Thr Asp Lys Thr Ala 385 390 395 400 Ala Gly His He Arg Ala Met Leu Gin Lys Cys Cys Pro Pro He Leu 405 410 415 Arg Gin Met Leu Ser Ala Arg Tyr Ser Gly Gly Leu Gin Glu Arg Leu 420 425 430 Trp Leu Pro Gly Ala Val Ala Val Pro Gly Val Val Lys Val Arg Asn 435 440 445 Ala Pro Ala Ser Ser He Val Thr Leu Ser Ser Asn Thr He Asn Thr 450 455 460 87 Ala Pro He Thr Ser Ala Ala Gin Thr Ala Thr Thr He Gly Arg Val 465 470 475 480 Ser Met Pro Thr Thr Gin Arg Gin Gly Ser Pro Gly Val Ser Ser Leu 485 490 495 Pro Gin He Arg Ala He Gin Ala Asn Gin Pro Ala Gin Lys Phe Val 500 505 510 He Val Thr Gin Asn Ser Pro Gin Gin Gly Gin Ala Lys Val Val Arg 515 520 525 Arg Gly Ser Ser Pro His Ser Val Val Leu Ser Ala Ala Ser Asn Ala 530 535 540 Ala Ser Ala Ser Asn Ser Asn Ser Ser Ser Ser Gly Ser Leu Leu Ala 545 550 555 560 Ala Ala Gin Arg Ser Ser Glu Asn Val Cys Val He Ala Gly Ser Glu 565 570 575 Ala Pro Ala Val Asp Gly He Thr Val Gin Ser Phe Arg Ala Ser 580 585 590 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1120 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: CDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 80..913 88 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: GATATGTACG TGCACAATTT CAATGGAATA AACAATCTTC TTGCAGCAAA GCCGACGTAA 60 ACATAATAAC TATAGAAGT ATG AGC GCA GAG AAG TCC GAT AAG GCC AAG ATC 112 Met Ser Ala Glu Lys Ser Asp Lys Ala Lys He 10 AGT GCC CAA ATC AAG CAC GTG CCG AAG GAC GCG CAG GTG ATC ATG TCC 160 Ser Ala Gin He Lys His Val Pro Lys Asp Ala Gin Val He Met Ser 15 20 25 ATC CTG AAG GAG CTG AAT GTC CAG GAG TAC GAG CCG CGC GTG GTC AAC 208 He Leu Lys Glu Leu Asn Val Gin Glu Tyr Glu Pro Arg Val Val Asn 30 35 40 CAA CTG CTG GAG TTC ACC TTC CGC TAT GTC ACC TGC ATT CTG GAC GAC 256 Gin Leu Leu Glu Phe Thr Phe Arg Tyr Val Thr Cys He Leu Asp Asp 45 50 55 GCC AAG GTA TAC GCC AAC CAT GCG CGC AAG AAG ACC ATC GAC TTG GAC 304 Ala Lys Val Tyr Ala Asn His Ala Arg Lys Lys Thr He Asp Leu Asp 60 65 70 75 GAC GTG CGT CTG GCC ACC GAG GTT ACG CTG GAC AAG AGC TTC ACC GGG 352 Asp Val Arg Leu Ala Thr Glu Val Thr Leu Asp Lys Ser Phe Thr Gly 89 80 85 90 CCG TTG GAG CGC CAC GTT CTA GCC AAG GTG GCC GAC GTG CGC AAC AGC 400 Pro Leu Glu Arg His Val Leu Ala Lys Val Ala Asp Val Arg Asn Ser 95 100 105 ATG CCC CTG CCA CCC ATT AAG CCG CAC TGC GGT CTC CGA CTG CCG CCC 448 Met Pro Leu Pro Pro He Lys Pro His Cys Gly Leu Arg Leu Pro Pro 110 115 120 GAC CGC TAC TGT CTC ACC GGC GTC AAC TAC AAA CTG CGG GCC ACT AAT 496 Asp Arg Tyr Cys Leu Thr Gly Val Asn Tyr Lys Leu Arg Ala Thr Asn 125 130 135 CAG CCC AAG AAA ATG ACC AAG TCG GCG GTG GAG GGC CGT CCA CTG AAG 544 Gin Pro Lys Lys Met Thr Lys Ser Ala Val Glu Gly Arg Pro Leu Lys 140 145 150 155 ACC GTC GTT AAG CCC GTC TCC AGC GCC AAT GGT CCG AAG AGG CCA CAC 592 Thr Val Val Lys Pro Val Ser Ser Ala Asn Gly Pro Lys Arg Pro His 160 165 170 TCC GTG GTG GCC AAG CAG CAG GTG GTG ACC ATT CCC AAG CCC GTC ATC 640 Ser Val Val Ala Lys Gin Gin Val Val Thr He Pro Lys Pro Val He 175 180 185 AAG TTT ACC ACC ACT ACG ACA ACG AAA ACG GTG GGC AGC TCC GGC GGA 688 90 Lys Phe Thr Thr Thr Thr Thr Thr Lys Thr Val Gly Ser Ser Gly Gly 190 195 200 TCT GGG GGC GGC GGT GGT CAG GAG GTT AAG AGC GAG AGC ACC GGC GCC 736 Ser Gly Gly Gly Gly Gly Gin Glu Val Lys Ser Glu Ser Thr Gly Ala 205 210 215 GGC GGA GAT CTC AAG ATG GAG GTG GAC AGC GAT GCG GCG GCC GTG GGC 784 Gly Gly Asp Leu Lys Met Glu Val Asp Ser Asp Ala Ala Ala Val Gly 220 225 230 235 AGC ATC GCT GGC GCA TCC GGT TCG GGA GCA GGA AGT GCC AGC GGA GGA 832 Ser He Ala Gly Ala Ser Gly Ser Gly Ala Gly Ser Ala Ser Gly Gly 240 245 250 GGA GGA GGA GGA GGA TCA TCT GGC GTT GGA GTG GCC GTC AAG CGG GAA 880 Gly Gly Gly Gly Gly Ser Ser Gly Val Gly Val Ala Val Lys Arg Glu 255 260 265 CGT GAG GAG GAG GAG TTT GAG TTT GTG ACC AAC TAGCGAAACG ACATCATTTA 933 Arg Glu Glu Glu Glu Phe Glu Phe Val Thr Asn 270 275 CCTTAAATTA ATATTCTTAA ATCAGACCAA AGCACTTGCA TTTGGTTGAG CGAACTGGGG 993 GTCTAAATTT CAACTCGAAT GTGAAGTCCC AAAAACCTTA GTATAGATTC GCCCGTTAAT 1053 91 CATTATGAAA TCTACGTTTT ATACACAAAT ACAACTACCA GATTTTCATA TTAAAAAAAA 1113 AAAAAAA 1120 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 278 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: Met Ser Ala Glu Lys Ser Asp Lys Ala Lys He Ser Ala Gin He Lys 1 5 10 15 His Val Pro Lys Asp Ala Gin Val He Met Ser He Leu Lys Glu Leu 20 25 30 Asn Val Gin Glu Tyr Glu Pro Arg Val Val Asn Gin Leu Leu Glu Phe 35 40 45 Thr Phe Arg Tyr Val Thr Cys He Leu Asp Asp Ala Lys Val Tyr Ala 50 55 60 Asn His Ala Arg Lys Lys Thr He Asp Leu Asp Asp Val Arg Leu Ala 65 70 75 80 Thr Glu Val Thr Leu Asp Lys Ser Phe Thr Gly Pro Leu Glu Arg His 85 90 95 Val Leu Ala Lys Val Ala Asp Val Arg Asn Ser Met Pro Leu Pro Pro 100 105 HO 92 He Lys Pro His Cys Gly Leu Arg Leu Pro Pro Asp Arg Tyr Cys Leu 115 120 125 Thr Gly Val Asn Tyr Lys Leu Arg Ala Thr Asn Gin Pro Lys Lys Met 130 135 140 Thr Lys Ser Ala Val Glu Gly Arg Pro Leu Lys Thr Val Val Lys Pro 145 150 155 160 Val Ser Ser Ala Asn Gly Pro Lys Arg Pro His Ser Val Val Ala Lys 165 170 175 Gin Gin Val Val Thr He Pro Lys Pro Val He Lys Phe Thr Thr Thr 180 185 190 Thr Thr Thr Lys Thr Val Gly Ser Ser Gly Gly Ser Gly Gly Gly Gly 195 200 205 Gly Gin Glu Val Lys Ser Glu Ser Thr Gly Ala Gly Gly Asp Leu Lys 210 215 220 Met Glu Val Asp Ser Asp Ala Ala Ala Val Gly Ser He Ala Gly Ala 225 230 235 240 Ser Gly Ser Gly Ala Gly Ser Ala Ser Gly Gly Gly Gly Gly Gly Gly 245 250 255 Ser Ser Gly Val Gly Val Ala Val Lys Arg Glu Arg Glu Glu Glu Glu 260 265 270 Phe Glu Phe Val Thr Asn 275 (2) INFORMATION FOR SEQ ID NO:10: 93 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5962 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 14..5692 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: TTATTTCCGG CAT ATG GGA CCC GGC TGC GAT TTG CTG CTG CGG ACA GCA 49 Met Gly Pro Gly Cys Asp Leu Leu Leu Arg Thr Ala 1 5 10 GCT ACC ATC ACT GCT GCC GCC ATC ATG TCA GAC ACG GAC AGC GAC GAA 97 Ala Thr He Thr Ala Ala Ala He Met Ser Asp Thr Asp Ser Asp Glu 15 20 25 GAT TCC GCT GGA GGC GGC CCA TTT TCT TTA GCG GGT TTC CTT TTC GGC 145 Asp Ser Ala Gly Gly Gly Pro Phe Ser Leu Ala Gly Phe Leu Phe Gly 30 35 40 AAC ATC AAT GGA GCC GGG CAG CTG GAG GGG GAA AGC GTC TTG GAT GAT 193 Asn He Asn Gly Ala Gly Gin Leu Glu Gly Glu Ser Val Leu Asp Asp 45 50 55 60 GAA TGT AAG AAG CAC TTG GCA GGC TTG GGG GCT TTG GGG CTG GGC AGC 241 Glu Cys Lys Lys His Leu Ala Gly Leu Gly Ala Leu Gly Leu Gly Ser 94 65 70 75 CTG ATC ACT GAA CTC ACG GCA AAT GAA GAA TTG ACC GGG ACT GAC GGT 289 Leu He Thr Glu Leu Thr Ala Asn Glu Glu Leu Thr Gly Thr Asp Gly 80 85 90 GCC TTG GTA AAT GAT GAA GGG TGG GTT AGG AGT ACA GAA GAT GCT GTG 337 Ala Leu Val Asn Asp Glu Gly Trp Val Arg Ser Thr Glu Asp Ala Val 95 100 105 GAC TAT TCA GAC ATC AAT GAG GTG GCA GAA GAT GAA AGC CGA AGA TAC 385 Asp Tyr Ser Asp He Asn Glu Val Ala Glu Asp Glu Ser Arg Arg Tyr 110 115 120 CAG CAG ACG ATG GGG AGC TTG CAG CCC CTT TGC CAC TCA GAT TAT GAT 433 Gin Gin Thr Met Gly Ser Leu Gin Pro Leu Cys His Ser Asp Tyr TGC AAG TTG 481 Glu Asp Asp Tyr Asp Ala Asp Cys Glu Asp He Asp Cys Lys Leu Met 145 150 155 CCT CCT CCA CCT CCA CCC CCG GGA CCA ATG AAG AAG GAT AAG GAC CAG 529 p GAT TCT ATT ACT GGT4GTG TCT GAA AAT GGA GAA GGC ATC ATC TTG CCC L 577 95 Asp Ser lie Thr Gly Val Ser Glu Asn Gly Glu Gly He lie Leu Pro 175 180 185 AAA GTG GAC TTC 625 Ser He He Ala Pro Ser Ser Leu Ala Ser Glu Lys Val Asp Phe Ser 190 195 200 AGT TCC TCT GAC TCA GAA TCT GAG ATG GGA CCT CAG GAA GCA ACA CAG 673 Ser Ser Ser Asp Ser Glu Ser Glu Met Gly Pro Gin Glu Ala Thr Gin 205 210 215 220 GCA GAA TCT GAA GAT GGA AAG CTG ACC CTT CCA TTG GCT GGG ATT ATG 721 Ala Glu Ser Glu Asp Gly Lys Leu Thr Leu Pro Leu Ala Gly He Met 225 230 235 CAG CAT GAT GCC ACC AAG CTG TTG CCA AGT GTC ACA GAA CTT TTT CCA 769 Gin His Asp Ala Thr Lys Leu Leu Pro Ser Val Thr Glu Leu Phe Pro 240 245 250 GAA TTT CGA CCT GGA AAG GTG TTA CGT TTT CTA CGT CTT TTT GGA CCA 817 Glu Phe Arg Pro Gly Lys Val Leu Arg Phe Leu Arg Leu Phe Gly Pro 255 260 265 GGG AAG AAT GTC CCA TCT GTT TGG CGG AGT GCT CGG AGA AAG AGG AAG 865 Gly Lys Asn Val Pro Ser Val Trp Arg Ser Ala Arg Arg Lys Arg Lys 270 275 280 96 AAG AAG CAC CGT GAG CTG ATA CAG GAA GAG CAG ATC CAG GAG GTG GAG 913 Lys Lys His Arg Glu Leu He Gin Glu Glu Gin He Gin Glu Val Glu 285 290 295 300 TGC TCA GTA GAA TCA GAA GTC AGC CAG AAG TCT TTG TGG AAC TAC GAC 961 Cys Ser Val Glu Ser Glu Val Ser Gin Lys Ser Leu Trp Asn Tyr Asp 305 310 315 TAC GCT CCA CCA CCA CCT CCA GAG CAG TGT CTC TCT GAT GAT GAA ATC 1009 Tyr Ala Pro Pro Pro Pro Pro Glu Gin Cys Leu Ser Asp Asp Glu He 320 325 330 ACG ATG ATG GCT CCT GTG GAG TCC AAA TTT TCC CAA TCA ACT GGA GAT 1057 Thr Met Met Ala Pro Val Glu Ser Lys Phe Ser Gin Ser Thr Gly Asp 335 340 345 ATA GAT AAA GTG ACA GAT ACC AAA CCA AGA GTG GCT GAG TGG CGT TAT 1105 He Asp Lys Val Thr Asp Thr Lys Pro Arg Val Ala Glu Trp Arg Tyr 350 355 360 GGG CCT GCC CGA CTG TGG TAT GAT &TG CTG GGT GTC CCT GAA GAT GGC —J 1153 Gly Pro Ala Arg Leu Trp Tyr Asp Met Leu Gly Val Pro Glu Asp Gly 365 370 375 380 AGT GGG TTT GAC TAT GGC TTC AAA CTG AGA AAG ACA GAA CAT GAA CCT 1201 Ser Gly Phe Asp Tyr Gly Phe Lys Leu Arg Lys Thr Glu His Glu Pro 9 7 385 390 395 GTG ATA AAA TCT AGA ATG ATA GAG GAA TTT AGG AAA CTT GAG GAA AAC 1249 Val He Lys Ser Arg Met He Glu Glu Phe Arg Lys Leu Glu Glu Asn 400 405 410 AAT GGC ACT GAT CTT CTG GCT GAT GAA AAC TTC CTG ATG GTG ACA CAG 1297 Asn Gly Thr Asp Leu Leu Ala Asp Glu Asn Phe Leu Met Val Thr Gin 415 420 425 CTG CAT TGG GAG GAT GAT ATC ATC TGG GAT GGG GAG GAT GTC AAA CAC 1345 Leu His Trp Glu Asp Asp He He Trp Asp Gly Glu Asp Val Lys His 430 435 440 AAA GGG ACA AAA CCT CAG CGT GCA AGC CTG GCA GGC TGG CTT CCT TCT 1393 Lys Gly Thr Lys Pro Gin Arg Ala Ser Leu Ala Gly Trp Leu Pro Ser 445 450 455 460 AGC ATG ACT AGG AAT GCG ATG GCT TAC AAT GTT CAG CAA GGT TTT GCA 1441 Ser Met Thr Arg Asn Ala Met Ala Tyr Asn Val Gin Gin Gly Phe Ala 465 470 475 GCC ACT CTT GAT GAT GAC AAA CCT TGG TAC TCC ATT TTT CCC ATT GAC 1489 Ala Thr Leu Asp Asp Asp Lys Pro Trp Tyr Ser He Phe Pro He Asp 480 485 490 AAT GAG GAT CTG GTA TAT GGA CGC TGG GAG GAC AAT ATC ATT TGG GAT 1537 98 Asn Glu Asp Leu Val Tyr Gly Arg Trp Glu Asp Asn He He Trp Asp 495 500 505 GCT CAG GCC ATG CCC CGG CTG TTG GAA CCT CCT GTT TTG ACA CTT GAT 1585 Ala Gin Ala Met Pro Arg Leu Leu Glu Pro Pro Val Leu Thr Leu Asp 510 515 520 CCC AAT GAT GAG AAC CTC ATT TTG GAA ATT CCT GAT GAG AAG GAA GAG 1633 Pro Asn Asp Glu Asn Leu He Leu Glu He Pro Asp Glu Lys Glu Glu 525 530 535 540 GCC ACC TCT AAC TCC CCC TCC AAG GAG AGT AAG AAG GAA TCA TCT CTG 1681 Ala Thr Ser Asn Ser Pro Ser Lys Glu Ser Lys Lys Glu Ser Ser Leu ' 545 550 555 AAG AAG AGT CGA ATT CTC TTA GGG AAA ACA GGA GTC ATC AAG GAG GAA 1729 Lys Lys Ser Arg He Leu Leu Gly Lys Thr Gly Val He Lys Glu Glu 560 565 570 CCA CAG CAG AAC ATG TCT CAG CCA GAA GTG AAA GAT CCA TGG AAT CTC 1777 Pro Gin Gin Asn Met Ser Gin Pro Glu Val Lys Asp Pro Trp Asn Leu 575 580 585 TCC AAT GAT GAG TAT TAT TAT CCC AAG CAA CAG GGT CTT CGA GGC ACC 1825 Ser Asn Asp Glu Tyr Tyr Tyr Pro Lys Gin Gin Gly Leu Arg Gly Thr 590 595 600 99 TTT GGA GGG AAT ATT ATC CAG CAT TCA ATT CCT GCT GTG GAA TTA CGG 1873 Phe Gly Gly Asn He He Gin His Ser He Pro Ala Val Glu Leu Arg 605 610 615 620 CAG CCC TTC TTT CCC ACC CAC ATG GGG CCC ATC AAA CTC CGG CAG TTC 1921 Gin Pro Phe Phe Pro Thr His Met Gly Pro He Lys Leu Arg Gin Phe 625 630 635 CAT CGC CCA CCT CTG AAA AAG TAC TCA TTT GGT GCA CTT TCT CAG CCA 1969 His Arg Pro Pro Leu Lys Lys Tyr Ser Phe Gly Ala Leu Ser Gin Pro 640 645 650 GGT CCC CAC TCA GTC CAA CCT TTG CTA AAG CAC ATC AAA AAA AAG GCC 2017 Gly Pro His Ser Val Gin Pro Leu Leu Lys His He Lys Lys Lys Ala 655 660 665 AAG ATG AGA GAA CAA GAG AGG CAA GCT TCA GGT GGT GGA GAG ATG TTT 2065 Lys Met Arg Glu Gin Glu Arg Gin Ala Ser Gly Gly Gly Glu Met Phe 670 675 680 TTT ATG CGC ACA CCT CAG GAC CTC ACA GGC AAA GAT GGT GAT CTT ATT 2113 Phe Met Arg Thr Pro Gin Asp Leu Thr Gly Lys Asp Gly Asp Leu He 685 690 695 700 CTT GCA GAA TAT AGT GAG GAA AAT GGA CCC TTA ATG ATG CAG GTT GGC 2161 Leu Ala Glu Tyr Ser Glu Glu Asn Gly Pro Leu Met Met Gin Val Gly 100 705 710 715 ATG GCA ACC AAG ATA AAG AAC TAT TAT AAA CGG AAA CCT GGA AAA GAT 2209 Met Ala Thr Lys He Lys Asn Tyr Tyr Lys Arg Lys Pro Gly Lys Asp 720 725 730 CCT GGA GCA CCA GAT TGT AAA TAT GGG GAA ACT GTT TAC TGC CAT ACA 2257 Pro Gly Ala Pro Asp Cys Lys Tyr Gly Glu Thr Val Tyr Cys His Thr 735 740 745 TCT CCT TTC CTG GGT TCT CTC CAT CCT GGC CAA TTG CTG CAA GCA TTT 2305 Ser Pro Phe Leu Gly Ser Leu His Pro Gly Gin Leu Leu Gin Ala Phe 750 755 760 GAG AAC AAC CTT TTT CGT GCT CCA ATT TAT CTT CAT AAG ATG CCA GAA 2353 Glu Asn Asn Leu Phe Arg Ala Pro He Tyr Leu His Lys Met Pro Glu 765 770 775 780 ACT GAT TTC TTG ATC ATT CGG ACA AGA CAG GGT TAC TAT ATT CGG GAA 2401 Thr Asp Phe Leu He He Arg Thr Arg Gin Gly Tyr Tyr He Arg Glu 785 790 795 TTA GTG GAT ATT TTT GTG GTT GGC CAG CAG TGT CCC TTG TTT GAA GTT 2449 Leu Val Asp He Phe Val Val Gly Gin Gin Cys Pro Leu Phe Glu Val 800 805 810 CCT GGG CCT AAC TCC AAA AGG GCC AAT ACG CAT ATT CGA GAC TTT CTA 2497 101 Pro Gly Pro Asn Ser Lys Arg Ala Asn Thr His He Arg Asp Phe Leu 815 820 825 CAG GTT TTT ATT TAC CGC CTT TTC TGG AAA AGT AAA GAT CGG CCA CGG 2545 Gin Val Phe He Tyr Arg Leu Phe Trp Lys Ser Lys Asp Arg Pro Arg 830 835 840 AGG ATA CGA ATG GAA GAT ATA AAA AAA GCC TTT CCT TCC CAT TCA GAA 2593 Arg He Arg Met Glu Asp He Lys Lys Ala Phe Pro Ser His Ser Glu 845 850 855 860 AGC AGC ATC CGG AAG AGG CTA AAG CTC TGC GCT GAC TTC AAA CGC ACA 2641 Ser Ser He Arg Lys Arg Leu Lys Leu Cys Ala Asp Phe Lys Arg Thr 865 870 875 GGG ATG GAC TCA AAC TGG TGG GTG CTT AAG TCT GAT TTT CGT TTA CCA 2689 Gly Met Asp Ser Asn Trp Trp Val Leu Lys Ser Asp Phe Arg Leu Pro 880 885 890 ACG GAA GAA GAG ATC AGA GCT ATG GTG TCA CCA GAG CAG TGC TGT GCT 2737 Thr Glu Glu Glu He Arg Ala Met Val Ser Pro Glu Gin Cys Cys Ala 895 900 905 TAT TAT AGC ATG ATA GCT GCA GAG CAA CGA CTG AAG GAT GCT GGC TAT 2785 Tyr Tyr Ser Met He Ala Ala Glu Gin Arg Leu Lys Asp Ala Gly Tyr 910 915 920 102 GGT GAG AAA TCC TTT TTT GCT CCA GAA GAA GAA AAT GAG GAA GAT TTC 2833 Gly Glu Lys Ser Phe Phe Ala Pro Glu Glu Glu Asn Glu Glu Asp Phe 925 930 935 940 CAG ATG AAG ATT GAT GAT GAA GTT CGC ACT GCC CCT TGG AAC ACC ACA 2881 Gin Met Lys He Asp Asp Glu Val Arg Thr Ala Pro Trp Asn Thr Thr 945 950 955 AGG GCC TTC ATT GCT GCC ATG AAG GGC AAG TGT CTG CTA GAG GTG ACT 2929 Arg Ala Phe He Ala Ala Met Lys Gly Lys Cys Leu Leu Glu Val Thr 960 965 970 GGG GTG GCA GAT CCC ACG GGG TGT GGT GAA GGA TTC TCC TAT GTG AAG 2977 Gly Val Ala Asp Pro Thr Gly Cys Gly Glu Gly Phe Ser Tyr Val Lys 975 980 985 ATT CCA AAC AAA CCA ACA CAG CAG AAG GAT GAT AAA GAA CCG CAG CCA 3025 He Pro Asn Lys Pro Thr Gin Gin Lys Asp Asp Lys Glu Pro Gin Pro 990 995 1000 GTG AAG AAG ACA GTG ACA GGA ACA GAT GCA GAC CTT CGT CGC CTT TCC 3073 Val Lys Lys Thr Val Thr Gly Thr Asp Ala Asp Leu Arg Arg Leu Ser 1005 1010 1015 1020 CTG AAA AAT GCC AAG CAA CTT CTA CGT AAA TTT GGT GTG CCT GAG GAA 3121 Leu Lys Asn Ala Lys Gin Leu Leu Arg Lys Phe Gly Val Pro Glu Glu 10 1025 1030 1035 GAG ATT AAA AAG TTG TCC CGC TGG GAA GTG ATT GAT GTG GTG CGC ACA 3169 Glu He Lys Lys Leu Ser Arg Trp Glu Val He Asp Val Val Arg Thr 1040 1045 1050 ATG TCA ACA GAA CAG GCT CGT TCT GGA GAG GGG CCC ATG AGT AAA TTT 3217 Met Ser Thr Glu Gin Ala Arg Ser Gly Glu Gly Pro Met Ser Lys Phe 1055 1060 1065 GCC CGT GGA TCA AGG TTT TCT GTG GCT GAG CAT CAA GAG CGT TAC AAA 3265 Ala Arg Gly Ser Arg Phe Ser Val Ala Glu His Gin Glu Arg Tyr Lys 1070 1075 1080 GAG GAA TGT CAG CGC ATC TTT GAC CTA CAG AAC AAG GTT CTG TCA TCA 3313 Glu Glu Cys Gin Arg He Phe Asp Leu Gin Asn Lys Val Leu Ser Ser 1085 1090 1095 1100 ACT GAA GTC TTA TCA ACT GAC ACA GAC AGC AGC TCA GCT GAA GAT AGT 3361 Thr Glu Val Leu Ser Thr Asp Thr Asp Ser Ser Ser Ala Glu Asp Ser 1105 1110 1115 GAC TTT GAA GAA ATG GGA AAG AAC ATT GAG AAC ATG TTG CAG AAC AAG 3409 Asp Phe Glu Glu Met Gly Lys Asn He Glu Asn Met Leu Gin Asn Lys 1120 1125 1130 AAA ACC AGC TCT CAG CTT TCA CGT GAA CGG GAG GAA CAG GAG CGG AAG 3457 1 0 4 Lys Thr Ser Ser Gin Leu Ser Arg Glu Arg Glu Glu Gin Glu Arg Lys 1135 1140 1145 GAA CTA CAG CGA ATG CTA CTG GCA GCA GGC TCA GCA GCA TCC GGA AAC 3505 Glu Leu Gin Arg Met Leu Leu Ala Ala Gly Ser Ala Ala Ser Gly Asn 1150 1155 1160 AAT CAC AGA GAT GAT GAC ACA GCT TCC GTG ACT AGC CTT AAC TCT TCT 3553 Asn His Arg Asp Asp Asp Thr Ala Ser Val Thr Ser Leu Asn Ser Ser 1165 1170 1175 1180 GCC ACT GGA CGC TGT CTC AAG ATT TAT CGC ACG TTT CGA GAT GAA GAG 3601 Ala Thr Gly Arg Cys Leu Lys He Tyr Arg Thr Phe Arg Asp Glu Glu 1185 1190 1195 GGG AAA GAG TAT GTT CGC TGT GAG ACA GTC CGA AAA CCA GCT GTC ATT 3649 Gly Lys Glu Tyr Val Arg Cys Glu Thr Val Arg Lys Pro Ala Val He 1200 1205 1210 GAT GCC TAT GTG CGC ATA CGG ACT ACA AAA GAT GAG GAA TTC ATT CGA 3697 Asp Ala Tyr Val Arg He Arg Thr Thr Lys Asp Glu Glu Phe He Arg 1215 1220 1225 AAA TTT GCC CTT TTT GAT GAA CAA CAT CGG GAA GAG ATG CGA AAA GAA 3745 Lys Phe Ala Leu Phe Asp Glu Gin His Arg Glu Glu Met Arg Lys Glu 1230 1235 1240 105 CGG CGG AGG ATT CAA GAG CAA CTG AGG CGG CTT AAG AGG AAC CAG GAA 3793 Arg Arg Arg He Gin Glu Gin Leu Arg Arg Leu Lys Arg Asn Gin Glu 1245 1250 1255 1260 AAG GAG AAG CTT AAG GGT CCT CCT GAG AAG AAG CCC AAG AAA ATG AAG 3841 Lys Glu Lys Leu Lys Gly Pro Pro Glu Lys Lys Pro Lys Lys Met Lys 1265 1270 1275 GAG CGT CCT GAC CTA AAA CTG AAA TGT GGG GCA TGT GGT GCC ATT GGA 3889 Glu Arg Pro Asp Leu Lys Leu Lys Cys Gly Ala Cys Gly Ala He Gly 1280 1285 1290 CAC ATG AGG ACT AAC AAA TTC TGC CCC CTC TAT TAT CAA ACA AAT GCG 3937 His Met Arg Thr Asn Lys Phe Cys Pro Leu Tyr Tyr Gin Thr Asn Ala 1295 1300 1305 CCA CCT TCC AAC CCT GTT GCC ATG ACA GAA GAA CAG GAG GAG GAG TTG 3985 Pro Pro Ser Asn Pro Val Ala Met Thr Glu Glu Gin Glu Glu Glu Leu 1310 1315 1320 GAA AAG ACA GTC ATT CAT AAT GAT AAT GAA GAA CTT ATC AAG GTT GAA 4033 Glu Lys Thr Val He His Asn Asp Asn Glu Glu Leu He Lys Val Glu 1325 1330 1335 1340 GGG ACC AAA ATT GTC TTG GGG AAA CAG CTA ATT GAG AGT GCG GAT GAG 4081 Gly Thr Lys He Val Leu Gly Lys Gin Leu He Glu Ser Ala Asp Glu 106 1345 1350 1355 GTT CGC AGA AAA TCT CTG GTT CTC AAG TTT CCT AAA CAG CAG CTT CCT 4129 Val Arg Arg Lys Ser Leu Val Leu Lys Phe Pro Lys Gin Gin Leu Pro 1360 1365 1370 CCA AAG AAG AAA CGG CGA GTT GGA ACC ACT GTT CAC TGT GAC TAT TTG 4177 Pro Lys Lys Lys Arg Arg Val Gly Thr Thr Val His Cys Asp Tyr Leu 1375 1380 1385 AAT AGA CCT CAT AAG TCC ATC CAC CGG CGC CGC ACA GAC CCT ATG GTG 4225 Asn Arg Pro His Lys Ser He His Arg Arg Arg Thr Asp Pro Met Val 1390 1395 1400 ACG CTG TCG TCC ATC TTG GAG TCT ATC ATC AAT GAC ATG AGA GAT CTT 4273 Thr Leu Ser Ser He Leu Glu Ser He He Asn Asp Met Arg Asp Leu 1405 1410 1415 1420 CCA AAT ACA TAC CCT TTC CAC ACT CCA GTC AAT GCA AAG GTT GTA AAG 4321 Pro Asn Thr Tyr Pro Phe His Thr Pro Val Asn Ala Lys Val Val Lys 1425 1430 1435 GAC TAC TAC AAA ATC ATC ACT CGG CCA ATG GAC CTA CAA ACA CTC CGC 4369 Asp Tyr Tyr Lys He He Thr Arg Pro Met Asp Leu Gin Thr Leu Arg 1440 1445 1450 GAA AAC GTG CGT AAA CGC CTC TAC CCA TCT CGG GAA GAG TTC AGA GAG 4417 107 Glu Asn Val Arg Lys Arg Leu Tyr Pro Ser Arg Glu Glu Phe Arg Glu 1455 1460 1465 CAT CTG GAG CTA ATT GTG AAA AAT AGT GCA ACC TAC AAT GGG CCA AAA 4465 His Leu Glu Leu He Val Lys Asn Ser Ala Thr Tyr Asn Gly Pro Lys 1470 1475 1480 CAC TCA TTG ACT CAG ATC TCT CAA TCC ATG CTG GAT CTC TGT GAT GAA 4513 His Ser Leu Thr Gin He Ser Gin Ser Met Leu Asp Leu Cys Asp Glu 1485 1490 1495 1500 AAA CTC AAA GAG AAA GAA GAC AAA TTA GCT CGC TTA GAG AAA GCT ATC 4561 Lys Leu Lys Glu Lys Glu Asp Lys Leu Ala Arg Leu Glu Lys Ala He 1505 1510 1515 AAC CCC TTG CTG GAT GAT GAT GAC CAA GTG GCG TTT TCT TTC ATT CTG 4609 Asn Pro Leu Leu Asp Asp Asp Asp Gin Val Ala Phe Ser Phe He Leu 1520 1525 1530 GAC AAC ATT GTC ACC CAG AAA ATG ATG GCA GTT CCA GAT TCT TGG CCA 4657 Asp Asn He Val Thr Gin Lys Met Met Ala Val Pro Asp Ser Trp Pro 1535 1540 1545 TTT CAT CAC CCA GTT AAT AAG AAA TTT GTT CCA GAT TAT TAC AAA GTG 4705 Phe His His Pro Val Asn Lys Lys Phe Val Pro Asp Tyr Tyr Lys Val 1550 1555 1560 108 ATT GTC AAT CCA ATG GAT TTA GAG ACC ATA CGT AAG AAC ATC TCC AAG 4753 He Val Asn Pro Met Asp Leu Glu Thr He Arg Lys Asn He Ser Lys 1565 1570 1575 1580 CAC AAG TAT CAG AGT CGG GAG AGC TTT CTG GAT GAT GTA AAC CTT ATT 4801 His Lys Tyr Gin Ser Arg Glu Ser Phe Leu Asp Asp Val Asn Leu He 1585 1590 1595 CTG GCC AAC AGT GTT AAG TAT AAT GGA CCT GAG AGT CAG TAT ACT AAG 4849 Leu Ala Asn Ser Val Lys Tyr Asn Gly Pro Glu Ser Gin Tyr Thr Lys 1600 1605 1610 ACT GCC CAG GAG ATT GTG AAC GTC TGT TAC CAG ACA TTG ACT GAG TAT 4897 Thr Ala Gin Glu He Val Asn Val Cys Tyr Gin Thr Leu Thr Glu Tyr 1615 1620 1625 GAT GAA CAT TTG ACT CAA CTT GAG AAG GAT ATT TGT ACT GCT AAA GAA 4945 Asp Glu His Leu Thr Gin Leu Glu Lys Asp He Cys Thr Ala Lys Glu 1630 1635 1640 GCA GCT TTG GAG GAA GCA GAA TTA GAA AGC CTG GAC CCA ATG ACC CCA 4993 Ala Ala Leu Glu Glu Ala Glu Leu Glu Ser Leu Asp Pro Met Thr Pro 1645 1650 1655 1660 GGG CCC TAC ACG CCT CAG CCT CCT GAT TTG TAT GAT ACC AAC ACA TCC 5041 Gly Pro Tyr Thr Pro Gin Pro Pro Asp Leu Tyr Asp Thr Asn Thr Ser 109 1665 1670 1675 CTC AGT ATG TCT CGA GAT GCC TCT GTA TTT CAA GAT GAG AGC AAT ATG 5089 Leu Ser Met Ser Arg Asp Ala Ser Val Phe Gin Asp Glu Ser Asn Met 1680 1685 1690 TCT GTC TTG GAT ATC CCC AGT GCC ACT CCA GAA AAG CAG GTA ACA CAG 5137 Ser Val Leu Asp He Pro Ser Ala Thr Pro Glu Lys Gin Val Thr Gin 1695 1700 1705 GAA GGT GAA GAT GGA GAT GGT GAT CTT GCA GAT GAA GAG GAA GGA ACT 5185 Glu Gly Glu Asp Gly Asp Gly Asp Leu Ala Asp Glu Glu Glu Gly Thr 1710 1715 1720 GTA CAA CAG CCT CAA GCC AGT GTC CTG TAT GAG GAT TTG CTT ATG TCT 5233 Val Gin Gin Pro Gin Ala Ser Val Leu Tyr Glu Asp Leu Leu Met Ser 1725 1730 1735 1740 GAA GGA GAA GAT GAT GAG GAA GAT GCT GGG AGT GAT GAA GAA GGA GAC 5281 Glu Gly Glu Asp Asp Glu Glu Asp Ala Gly Ser Asp Glu Glu Gly Asp 1745 1750 1755 AAT CCT TTC TCT GCT ATC CAG CTG AGT GAA AGT GGA AGT GAC TCT GAT 5329 Asn Pro Phe Ser Ala He Gin Leu Ser Glu Ser Gly Ser Asp Ser Asp 1760 1765 1770 GTG GGA TCT GGT GGA ATA AGA CCC AAA CAA CCC CGC ATG CTT CAG GAG 5377 110 Val Gly Ser Gly Gly He Arg Pro Lys Gin Pro Arg Met Leu Gin Glu 1775 1780 1785 AAC ACA AGG ATG GAC ATG GAA AAT GAA GAA AGC ATG ATG TCC TAT GAG 5425 Asn Thr Arg Met Asp Met Glu Asn Glu Glu Ser Met Met Ser Tyr Glu 1790 1795 1800 GGA GAC GGT GGG GAG GCT TCC CAT GGT TTG GAG GAT AGC AAC ATC AGT 5473 Gly Asp Gly Gly Glu Ala Ser His Gly Leu Glu Asp Ser Asn He Ser 1805 1810 1815 1820 TAT GGG AGC TAT GAG GAG CCT GAT CCC AAG TCG AAC ACC CAA GAC ACA 5521 Tyr Gly Ser Tyr Glu Glu Pro Asp Pro Lys Ser Asn Thr Gin Asp Thr 1825 1830 1835 AGC TTC AGC AGC ATC GGT GGG TAT GAG GTA TCA GAG GAG GAA GAA GAT 5569 Ser Phe Ser Ser He Gly Gly Tyr Glu Val Ser Glu Glu Glu Glu Asp 1840 1845 1850 GAG GAG GAG GAA GAG CAG CGC TCT GGG CCG AGC GTA CTA AGC CAG GTC 5617 Glu Glu Glu Glu Glu Gin Arg Ser Gly Pro Ser Val Leu Ser Gin Val 1855 1860 1865 CAC CTG TCA GAG GAC GAG GAG GAC AGT GAG GAT TTC CAC TCC ATT GCT 5665 His Leu Ser Glu Asp Glu Glu Asp Ser Glu Asp Phe His Ser He Ala 1870 1875 1880 111 GGG GAC AGT GAC TTG GAC TCT GAT GAA TGAGGCTTCC TTTGGGCCTC 5712 Gly Asp Ser Asp Leu Asp Ser Asp Glu 1885 1890 CTTGGTCAGC CTTCCCTGTT CTCCAGCCTA GGTGGTTCAC CTTTCCCCAA TTTGTTCATA 5772 TTTGTACAGT ATCTGATCCT GAAATCATGA AATTAACTAA CACCTTAGCC TTTTTAAAAG 5832 TAGTAAGTAA ATGATAATAA ATCACCTCTC CTAATCTTCC TGGGGCAATG TCACCCTTTG 5892 ATTTAAAACA AAGCAACCCC CTTTCCCCTA CCACTACGGA AAAGAGCAAG CTCATTTTTC 5952 CGTGTCCTCC 5962 (2) INFORMATION FOR SEQ ID NO: 11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1893 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: Met Gly Pro Gly Cys Asp Leu Leu Leu Arg Thr Ala Ala Thr He Thr 1 5 10 15 Ala Ala Ala He Met Ser Asp Thr Asp Ser Asp Glu Asp Ser Ala Gly 20 25 30 Gly Gly Pro Phe Ser Leu Ala Gly Phe Leu Phe Gly Asn He Asn Gly 35 40 45 112 Ala Gly Gin Leu Glu Gly Glu Ser Val Leu Asp Asp Glu Cys Lys Lys 50 55 60 His Leu Ala Gly Leu Gly Ala Leu Gly Leu Gly Ser Leu He Thr Glu 65 70 75 80 Leu Thr Ala Asn Glu Glu Leu Thr Gly Thr Asp Gly Ala Leu Val Asn 85 90 95 Asp Glu Gly Trp Val Arg Ser Thr Glu Asp Ala Val Asp Tyr Ser Asp 100 105 110 He Asn Glu Val Ala Glu Asp Glu Ser Arg Arg Tyr Gin Gin Thr Met 115 120 125 Gly Ser Leu Gin Pro Leu Cys His Ser Asp Tyr Asp Glu Asp Asp Tyr 130 135 140 Asp Ala Asp Cys Glu Asp He Asp Cys Lys Leu Met Pro Pro Pro Pro 145 150 155 160 Pro Pro Pro Gly Pro Met Lys Lys Asp Lys Asp Gin Asp Ser He Thr 165 170 175 Gly Val Ser Glu Asn Gly Glu Gly He He Leu Pro Ser He He Ala 180 185 190 Pro Ser Ser Leu Ala Ser Glu Lys Val Asp Phe Ser Ser Ser Ser Asp 195 200 205 Ser Glu Ser Glu Met Gly Pro Gin Glu Ala Thr Gin Ala Glu Ser Glu 210 215 220 113 Asp Gly Lys Leu Thr Leu Pro Leu Ala Gly He Met Gin His Asp Ala 225 230 235 240 Thr Lys Leu Leu Pro Ser Val Thr Glu Leu Phe Pro Glu Phe Arg Pro 245 250 255 Gly Lys Val Leu Arg Phe Leu Arg Leu Phe Gly Pro Gly Lys Asn Val 260 265 270 Pro Ser Val Trp Arg Ser Ala Arg Arg Lys Arg Lys Lys Lys His Arg 275 280 285 Glu Leu He Gin Glu Glu Gin He Gin Glu Val Glu Cys Ser Val Glu 290 295 300 Ser Glu Val Ser Gin Lys Ser Leu Trp Asn Tyr Asp Tyr Ala Pro Pro 305 310 315 320 Pro Pro Pro Glu Gin Cys Leu Ser Asp Asp Glu He Thr Met Met Ala 325 330 335 Pro Val Glu Ser Lys Phe Ser Gin Ser Thr Gly Asp He Asp Lys Val 340 345 350 Thr Asp Thr Lys Pro Arg Val Ala Glu Trp Arg Tyr Gly Pro Ala Arg 355 360 365 Leu Trp Tyr Asp Met Leu Gly Val Pro Glu Asp Gly Ser Gly Phe Asp 370 375 380 Tyr Gly Phe Lys Leu Arg Lys Thr Glu His Glu Pro Val He Lys Ser 385 390 395 400 114 Arg Met He Glu Glu Phe Arg Lys Leu Glu Glu Asn Asn Gly Thr Asp 405 410 415 Leu Leu Ala Asp Glu Asn Phe Leu Met Val Thr Gin Leu His Trp Glu 420 425 430 Asp Asp He He Trp Asp Gly Glu Asp Val Lys His Lys Gly Thr Lys 435 440 445 Pro Gin Arg Ala Ser Leu Ala Gly Trp Leu Pro Ser Ser Met Thr Arg 450 455 460 Asn Ala Met Ala Tyr Asn Val Gin Gin Gly Phe Ala Ala Thr Leu Asp 465 470 475 480 Asp Asp Lys Pro Trp Tyr Ser He Phe Pro He Asp Asn Glu Asp Leu 485 490 495 Val Tyr Gly Arg Trp Glu Asp Asn He He Trp Asp Ala Gin Ala Met 500 505 510 Pro Arg Leu Leu Glu Pro Pro Val Leu Thr Leu Asp Pro Asn Asp Glu 515 520 525 Asn Leu He Leu Glu He Pro Asp Glu Lys Glu Glu Ala Thr Ser Asn 530 535 540 Ser Pro Ser Lys Glu Ser Lys Lys Glu Ser Ser Leu Lys Lys Ser Arg 545 550 555 560 He Leu Leu Gly Lys Thr Gly Val He Lys Glu Glu Pro Gin Gin Asn 565 570 575 115 Met Ser Gin Pro Glu Val Lys Asp Pro Trp Asn Leu Ser Asn Asp Glu 580 585 590 Tyr Tyr Tyr Pro Lys Gin Gin Gly Leu Arg Gly Thr Phe Gly Gly Asn 595 600 605 He He Gin His Ser He Pro Ala Val Glu Leu Arg Gin Pro Phe Phe 610 615 620 Pro Thr His Met Gly Pro He Lys Leu Arg Gin Phe His Arg Pro Pro 625 630 635 640 Leu Lys Lys Tyr Ser Phe Gly Ala Leu Ser Gin Pro Gly Pro His Ser 645 650 655 Val Gin Pro Leu Leu Lys His He Lys Lys Lys Ala Lys Met Arg Glu 660 665 670 Gin Glu Arg Gin Ala Ser Gly Gly Gly Glu Met Phe Phe Met Arg Thr 675 680 685 Pro Gin Asp Leu Thr Gly Lys Asp Gly Asp Leu He Leu Ala Glu Tyr 690 695 700 Ser Glu Glu Asn Gly Pro Leu Met Met Gin Val Gly Met Ala Thr Lys 705 710 715 720 He Lys Asn Tyr Tyr Lys Arg Lys Pro Gly Lys Asp Pro Gly Ala Pro 725 730 735 Asp Cys Lys Tyr Gly Glu Thr Val Tyr Cys His Thr Ser Pro Phe Leu 740 745 750 116 Gly Ser Leu His Pro Gly Gin Leu Leu Gin Ala Phe Glu Asn Asn Leu 755 760 765 Phe Arg Ala Pro He Tyr Leu His Lys Met Pro Glu Thr Asp Phe Leu 770 775 780 He He Arg Thr Arg Gin Gly Tyr Tyr He Arg Glu Leu Val Asp He 785 790 795 800 Phe Val Val Gly Gin Gin Cys Pro Leu Phe Glu Val Pro Gly Pro Asn 805 810 815 Ser Lys Arg Ala Asn Thr His He Arg Asp Phe Leu Gin Val Phe He 820 825 830 Tyr Arg Leu Phe Trp Lys Ser Lys Asp Arg Pro Arg Arg He Arg Met 835 840 845 Glu Asp He Lys Lys Ala Phe Pro Ser His Ser Glu Ser Ser He Arg 850 855 860 Lys Arg Leu Lys Leu Cys Ala Asp Phe Lys Arg Thr Gly Met Asp Ser 865 870 875 880 Asn Trp Trp Val Leu Lys Ser Asp Phe Arg Leu Pro Thr Glu Glu Glu 885 890 895 He Arg Ala Met Val Ser Pro Glu Gin Cys Cys Ala Tyr Tyr Ser Met 900 905 910 He Ala Ala Glu Gin Arg Leu Lys Asp Ala Gly Tyr Gly Glu Lys Ser 915 920 925 117 Phe Phe Ala Pro Glu Glu Glu Asn Glu Glu Asp Phe Gin Met Lys He 930 935 940 Asp Asp Glu Val Arg Thr Ala Pro Trp Asn Thr Thr Arg Ala Phe He 945 950 955 960 Ala Ala Met Lys Gly Lys Cys Leu Leu Glu Val Thr Gly Val Ala Asp 965 970 975 Pro Thr Gly Cys Gly Glu Gly Phe Ser Tyr Val Lys He Pro Asn Lys 980 985 990 Pro Thr Gin Gin Lys Asp Asp Lys Glu Pro Gin Pro Val Lys Lys Thr 995 1000 1005 Val Thr Gly Thr Asp Ala Asp Leu Arg Arg Leu Ser Leu Lys Asn Ala 1010 1015 1020 Lys Gin Leu Leu Arg Lys Phe Gly Val Pro Glu Glu Glu He Lys Lys 1025 1030 1035 1040 Leu Ser Arg Trp Glu Val He Asp Val Val Arg Thr Met Ser Thr Glu 1045 1050 1055 Gin Ala Arg Ser Gly Glu Gly Pro Met Ser Lys Phe Ala Arg Gly Ser 1060 1065 1070 Arg Phe Ser Val Ala Glu His Gin Glu Arg Tyr Lys Glu Glu Cys Gin 1075 1080 1085 Arg He Phe Asp Leu Gin Asn Lys Val Leu Ser Ser Thr Glu Val Leu 1090 1095 1100 118 Ser Thr Asp Thr Asp Ser Ser Ser Ala Glu Asp Ser Asp Phe Glu Glu 1105 1110 1115 1120 Met Gly Lys Asn He Glu Asn Met Leu Gin Asn Lys Lys Thr Ser Ser 1125 1130 1135 Gin Leu Ser Arg Glu Arg Glu Glu Gin Glu Arg Lys Glu Leu Gin Arg 1140 1145 1150 Met Leu Leu Ala Ala Gly Ser Ala Ala Ser Gly Asn Asn His Arg Asp 1155 1160 1165 Asp Asp Thr Ala Ser Val Thr Ser Leu Asn Ser Ser Ala Thr Gly Arg 1170 1175 1180 Cys Leu Lys He Tyr Arg Thr Phe Arg Asp Glu Glu Gly Lys Glu Tyr 1185 1190 1195 1200 Val Arg Cys Glu Thr Val Arg Lys Pro Ala Val He Asp Ala Tyr Val 1205 1210 ! 1215 Arg He Arg Thr Thr Lys Asp Glu Glu Phe He Arg Lys Phe Ala Leu 1220 1225 1230 Phe Asp Glu Gin His Arg Glu Glu Met Arg Lys Glu Arg Arg Arg He 1235 1240 1245 Gin Glu Gin Leu Arg Arg Leu Lys Arg Asn Gin Glu Lys Glu Lys Leu 1250 1255 1260 Lys Gly Pro Pro Glu Lys Lys Pro Lys Lys Met Lys Glu Arg Pro Asp 1265 1270 1275 1280 119 Leu Lys Leu Lys Cys Gly Ala Cys Gly Ala He Gly His Met Arg Thr 1285 1290 1295 Asn Lys Phe Cys Pro Leu Tyr Tyr Gin Thr Asn Ala Pro Pro Ser Asn 1300 1305 1310 Pro Val Ala Met Thr Glu Glu Gin Glu Glu Glu Leu Glu Lys Thr Val 1315 1320 1325 He His Asn Asp Asn Glu Glu Leu He Lys Val Glu Gly Thr Lys He 1330 1335 1340 Val Leu Gly Lys Gin Leu He Glu Ser Ala Asp Glu Val Arg Arg Lys 1345 1350 1355 1360 Ser Leu Val Leu Lys Phe Pro Lys Gin Gin Leu Pro Pro Lys Lys Lys 1365 1370 1375 Arg Arg Val Gly Thr Thr Val His Cys Asp Tyr Leu Asn Arg Pro His 1380 1385 1390 Lys Ser He His Arg Arg Arg Thr Asp Pro Met Val Thr Leu Ser Ser 1395 1400 1405 He Leu Glu Ser He He Asn Asp Met Arg Asp Leu Pro Asn Thr Tyr 1410 1415 1420 Pro Phe His Thr Pro Val Asn Ala Lys Val Val Lys Asp Tyr Tyr Lys 1425 1430 1435 1440 He He Thr Arg Pro Met Asp Leu Gin Thr Leu Arg Glu Asn Val Arg 1445 1450 1455 120 Lys Arg Leu Tyr Pro Ser Arg Glu Glu Phe Arg Glu His Leu Glu Leu 1460 1465 1470 He Val Lys Asn Ser Ala Thr Tyr Asn Gly Pro Lys His Ser Leu Thr 1475 1480 1485 Gin He Ser Gin Ser Met Leu Asp Leu Cys Asp Glu Lys Leu Lys Glu 1490 1495 1500 Lys Glu Asp Lys Leu Ala Arg Leu Glu Lys Ala He Asn Pro Leu Leu 1505 1510 1515 1520 Asp Asp Asp Asp Gin Val Ala Phe Ser Phe He Leu Asp Asn He Val 1525 1530 1535 Thr Gin Lys Met Met Ala Val Pro Asp Ser Trp Pro Phe His His Pro 1540 1545 1550 Val Asn Lys Lys Phe Val Pro Asp Tyr Tyr Lys Val He Val Asn Pro 1555 1560 1565 Met Asp Leu Glu Thr He Arg Lys Asn He Ser Lys His Lys Tyr Gin 1570 1575 1580 Ser Arg Glu Ser Phe Leu Asp Asp Val Asn Leu He Leu Ala Asn Ser 1585 1590 1595 1600 Val Lys Tyr Asn Gly Pro Glu Ser Gin Tyr Thr Lys Thr Ala Gin Glu 1605 1610 1615 He Val Asn Val Cys Tyr Gin Thr Leu Thr Glu Tyr Asp Glu His Leu 1620 1625 1630 121 Thr Gin Leu Glu Lys Asp He Cys Thr Ala Lys Glu Ala Ala Leu Glu 1635 1640 1645 Glu Ala Glu Leu Glu Ser Leu Asp Pro Met Thr Pro Gly Pro Tyr Thr 1650 1655 1660 Pro Gin Pro Pro Asp Leu Tyr Asp Thr Asn Thr Ser Leu Ser Met Ser 1665 1670 1675 1680 Arg Asp Ala Ser Val Phe Gin Asp Glu Ser Asn Met Ser Val Leu Asp 1685 1690 1695 He Pro Ser Ala Thr Pro Glu Lys Gin Val Thr Gin Glu Gly Glu Asp 1700 1705 1710 Gly Asp Gly Asp Leu Ala Asp Glu Glu Glu Gly Thr Val Gin Gin Pro 1715 1720 1725 Gin Ala Ser Val Leu Tyr Glu Asp Leu Leu Met Ser Glu Gly Glu Asp 1730 1735 1740 Asp Glu Glu Asp Ala Gly Ser Asp Glu Glu Gly Asp Asn Pro Phe Ser 1745 1750 1755 1760 Ala He Gin Leu Ser Glu Ser Gly Ser Asp Ser Asp Val Gly Ser Gly 1765 1770 1775 Gly He Arg Pro Lys Gin Pro Arg Met Leu Gin Glu Asn Thr Arg Met 1780 1785 1790 Asp Met Glu Asn Glu Glu Ser Met Met Ser Tyr Glu Gly Asp Gly Gly 1795 1800 1805 1 2 2 Glu Ala Ser His Gly Leu Glu Asp Ser Asn He Ser Tyr Gly Ser Tyr 1810 1815 1820 Glu Glu Pro Asp Pro Lys Ser Asn Thr Gin Asp Thr Ser Phe Ser Ser 1825 1830 1835 1840 He Gly Gly Tyr Glu Val Ser Glu Glu Glu Glu Asp Glu Glu Glu Glu 1845 1850 1855 Glu Gin Arg Ser Gly Pro Ser Val Leu Ser Gin Val His Leu Ser Glu 1860 1865 1870 Asp Glu Glu Asp Ser Glu Asp Phe His Ser He Ala Gly Asp Ser Asp 1875 1880 1885 Leu Asp Ser Asp Glu 1890 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3182 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 972..3002 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: CGAGTTTTTT TTTTTTTTTT TTTTACAAGA GCACAAATCC ACATTTATTT ATTGATTTTT 60 CGTTAGTTTA AATCCTTGAG GGGTACAGCA TCACTCGGAT TCTGTGTCCA ATGGCCTTAG 120 1 2 3 CAGGAAGATT GCTTCGGAAT TTGGCACGAA CCATGCCACT GTTTCCATGG GCCCGAGTTA 180 CTTTTCCCCA GATGACTCTG GTTTTGTTTG GTTTGCCGCC AGGAGTGACT GTGTTGTTCT 240 TTGCTTTATA TACATAAGCG CATCTCTTGC CCAAATAGAA TTCTGTTTCA TCTCGGGCGT 300 AAACACCTTC AATTTTAAGA AGAGCTGTGT GCTCCCTTTG GTTCCGGAGA CCCCGCTTAT 360 AGCCAGCAAA AATGGCCTTG GACCACAGCC TTCCAGACAT AGTTCCTTTT AGAAGTCCCG 420 TTCCCAGCAG GCCTCCACAG GAGCCAAGAT GGCGCCGAGC CGGGTGAGCA GCGTCTCGGC 480 TGCCGCTAGA GTTTTCCTGC TCCCCGCGCT CGGGTGGCGG GGGCGGGTCT GAGTGGTACC 540 CCGGAGGAGA CCCTTTGAAG GTCCCTTGTG GGGACTGGAA AGAGGACGGT TGGTTGTGTG 600 TCTGTGCTCG TGGGGACCCC GTGTGTGTGC CTGCATTGGA GAGATGTTGC AGGAGATGGG 660 GTGGGCTCTC TGAACCTCCT TTCGCGCTGC CCGGGGATCT TCGACCTGCT TCTCTGCTGG 720 GATCTCGCTT AAGTTAACCC TTCCCTGGGA CGCCTTCCTG CCGCCTCCAC TGATCTGAGG 780 AGATCCTGTG ACTGTAGCGT GTTTTATGAG CCTTTACTGG CAGAGGGTAC CGCCGGGTAT 840 TGAAGGATTC GTAGGAGTTC GCCAGGGAAG TGGGACACGA CCCCCTCTTG TAAACCCGGC 900 GCCAGGCACA GAGGTCTCGG TCTCTCCACC GGGGGCTTCA TCCTTCCAGG GAGGAGAAGA 124 960 GGGACTCCAG A ATG GCT GAG GAG AAG AAG CTG AAG CTT AGC AAC ACT GTG 1010 Met Ala Glu Glu Lys Lys Leu Lys Leu Ser Asn Thr Val 1 5 10 CTG CCC TCG GAG TCC ATG AAG GTG GTG GCT GAA TCC ATG GGC ATC GCC 1058 Leu Pro Ser Glu Ser Met Lys Val Val Ala Glu Ser Met Gly He Ala 15 20 25 CAG ATT CAG GAG GAG ACC TGC CAG CTG CTA ACG GAT GAG GTC AGC TAC 1106 Gin He Gin Glu Glu Thr Cys Gin Leu Leu Thr Asp Glu Val Ser Tyr 30 35 40 45 CGC ATC AAA GAG ATC GCA CAG GAT GCC TTG AAG TTC ATG CAC ATG GGG 1154 Arg He Lys Glu He Ala Gin Asp Ala Leu Lys Phe Met His Met Gly 50 55 60 AAG CGG CAG AAG CTC ACC ACC AGT GAC ATT GAC TAC GCC TTG AAG CTA 1202 Lys Arg Gin Lys Leu Thr Thr Ser Asp He Asp Tyr Ala Leu Lys Leu 65 70 75 AAG AAT GTC GAG CCA CTC TAT GGC TTC CAC GCC CAG GAC TTC ATT CCT 1250 Lys Asn Val Glu Pro Leu Tyr Gly Phe His Ala Gin Asp Phe He Pro 80 85 90 TTC CGC TTC GCC TCT GGT GGG GGC CGG GAG CTT TAC TTC TAT GAG GAG 125 1298 Phe Arg Phe Ala Ser Gly Gly Gly Arg Glu Leu Tyr Phe Tyr Glu Glu 95 100 105 AAG GAG GTT GAT CTG AGC GAC ATC ATC AAT ACC CCT CTG CCC CGG GTG 1346 Lys Glu Val Asp Leu Ser Asp He He Asn Thr Pro Leu Pro Arg Val 110 115 120 125 CCC CTG GAC GTC TGC CTC AAA GCT CAT TGG CTG AGC ATC GAG GGC TGC 1394 Pro Leu Asp Val Cys Leu Lys Ala His Trp Leu Ser He Glu Gly Cys 130 135 140 CAG CCA GCT ATC CCC GAG AAC CCG CCC CCA GCT CCC AAA GAG CAA CAG 1442 Gin Pro Ala He Pro Glu Asn Pro Pro Pro Ala Pro Lys Glu Gin Gin 145 150 155 AAG GCT GAA GCC ACA GAA CCC CTG AAG TCA GCC AAG CCA GGC CAG GAG 1490 Lys Ala Glu Ala Thr Glu Pro Leu Lys Ser Ala Lys Pro Gly Gin Glu 160 165 170 GAA GAC GGA CCC CTG AAG GGC AAA GGT CAA GGG GCC ACC ACA GCC GAC 1538 Glu Asp Gly Pro Leu Lys Gly Lys Gly Gin Gly Ala Thr Thr Ala Asp 175 180 185 GGC AAA GGG AAA GAG AAG AAG GCG CCG CCC TTG CTG GAG GGG GCC CCC 1586 Gly Lys Gly Lys Glu Lys Lys Ala Pro Pro Leu Leu Glu Gly Ala Pro 190 195 200 205 126 TTG CGA CTG AAG CCC CGG AGC ATC CAC GAG TTG TCT GTG GAG CAG CAG 1634 Leu Arg Leu Lys Pro Arg Ser He His Glu Leu Ser Val Glu Gin Gin 210 215 220 CTC TAC TAC AAG GAG ATC ACC GAG GCC TGC GTG GGC TCC TGC GAG GCC 1682 Leu Tyr Tyr Lys Glu He Thr Glu Ala Cys Val Gly Ser Cys Glu Ala 225 230 235 AAG AGG GCG GAA GCC CTG CAA AGC ATT GCC ACG GAC CCT GGA CTG TAT 1730 Lys Arg Ala Glu Ala Leu Gin Ser He Ala Thr Asp Pro Gly Leu Tyr 240 245 250 CAG ATG CTG CCA CGG TTC AGT ACC TTT ATC TCG GAG GGG GTC CGT GTG 1778 Gin Met Leu Pro Arg Phe Ser Thr Phe He Ser Glu Gly Val Arg Val 255 260 265 AAC GTG GTT CAG AAC AAC CTG GCC CTA CTC ATC TAC CTG ATG CGT ATG 1826 Asn Val Val Gin Asn Asn Leu Ala Leu Leu He Tyr Leu Met Arg Met 270 275 280 285 GTG AAA GCG CTG ATG GAC AAC CCC ACG CTC TAT CTA GAA AAA TAC GTC 1874 Val Lys Ala Leu Met Asp Asn Pro Thr Leu Tyr Leu Glu Lys Tyr Val 290 295 300 CAT GAG CTG ATT CCA GCT GTG ATG ACC TGC ATC GTG AGC AGA CAG TTG 1922 His Glu Leu He Pro Ala Val Met Thr Cys He Val Ser Arg Gin Leu 127 305 310 315 TGC CTG CGA CCA GAT GTG GAC AAT CAC TGG GCA CTC CGA GAC TTT GCT 1970 Cys Leu Arg Pro Asp Val Asp Asn His Trp Ala Leu Arg Asp Phe Ala 320 325 330 GCC CGC CTG GTG GCC CAG ATC TGC AAG CAT TTT AGC ACA ACC ACT AAC 2018 Ala Arg Leu Val Ala Gin He Cys Lys His Phe Ser Thr Thr Thr Asn 335 340 345 AAC ATC CAG TCC CGG ATC ACC AAG ACC TTC ACC AAG AGC TGG GTG GAC 2066 Asn He Gin Ser Arg He Thr Lys Thr Phe Thr Lys Ser Trp Val Asp 350 355 360 365 GAG AAG ACG CCC TGG ACG ACT CGT TAT GGC TCC ATC GCA GGC TTG GCT 2114 Glu Lys Thr Pro Trp Thr Thr Arg Tyr Gly Ser He Ala Gly Leu Ala 370 375 380 GAG CTG GGA CAC GAT GTT ATC AAG ACT CTG ATT CTG CCC CGG CTG CAG 2162 Glu Leu Gly His Asp Val He Lys Thr Leu He Leu Pro Arg Leu Gin 385 390 395 ACC TTC ACC AAG AGC TGG GTG GAC GAG AAG ACG CCC TGG ACG ACT CGT 2210 Thr Phe Thr Lys Ser Trp Val Asp Glu Lys Thr Pro Trp Thr Thr Arg 400 405 410 TAT GGC TCC AGG ATT GGA GCA GAC CAT GTG CAG AGC CTC CTG CTG AAA 2258 128 Tyr Gly Ser Arg He Gly Ala Asp His Val Gin Ser Leu Leu Leu Lys 415 420 425 CAC TGT GCT CCT GTT CTG GCA AAG CTG CGC CCA CCG CCT GAC AAT CAG 2306 His Cys Ala Pro Val Leu Ala Lys Leu Arg Pro Pro Pro Asp Asn Gin 430 435 440 445 GAC GCC TAT CGG GCA GAA TTC GGG TCC CTT GGG CCC CTC CTC TGC TCC 2354 Asp Ala Tyr Arg Ala Glu Phe Gly Ser Leu Gly Pro Leu Leu Cys Ser 450 455 460 CAG GTG GTC AAG GCT CGG GCC CAG GCT GCT CTG CAG GCT CAG CAG GTC 2402 Gin Val Val Lys Ala Arg Ala Gin Ala Ala Leu Gin Ala Gin Gin Val 465 470 475 AAC AGG ACC ACT CTG ACC ATC ACG CAG CCC CGG CCC ACG CTG ACC CTC 2450 Asn Arg Thr Thr Leu Thr He Thr Gin Pro Arg Pro Thr Leu Thr Leu 480 485 490 TCG CAG GCC CCA CAG CCT GGC CCT CGC ACC CCT GGC TTG CTG AAG GTT 2498 Ser Gin Ala Pro Gin Pro Gly Pro Arg Thr Pro Gly Leu Leu Lys Val 495 500 505 CCT GGC TCC ATC GCA CTT CCT GTC CAG ACA CTG GTG TCT GCA CGA GCG 2546 Pro Gly Ser He Ala Leu Pro Val Gin Thr Leu Val Ser Ala Arg Ala 510 515 520 525 129 GCT GCC CCA CCA CAG CCT TCC CCT CCT CCC ACC AAG TTT ATT GTA ATG 2594 Ala Ala Pro Pro Gin Pro Ser Pro Pro Pro Thr Lys Phe He Val Met 530 535 540 TCA TCG TCC TCC AGC GCC CCA TCC ACC CAG CAG GTC CTG TCC CTC AGC 2642 Ser Ser Ser Ser Ser Ala Pro Ser Thr Gin Gin Val Leu Ser Leu Ser 545 550 555 ACC TCG GCC CCC GGC TCA GGT TCC ACC ACC ACT TCG CCC GTC ACC ACC 2690 Thr Ser Ala Pro Gly Ser Gly Ser Thr Thr Thr Ser Pro Val Thr Thr 560 565 570 ACC GTC CCC AGC GTG CAG CCC ATC GTC AAG TTG GTC TCC ACC GCC ACC 2738 Thr Val Pro Ser Val Gin Pro He Val Lys Leu Val Ser Thr Ala Thr 575 580 585 ACC GCA CCC CCC AGC ACT GCT CCC TCT GGT CCT GGG AGT GTC CAG AAG 2786 Thr Ala Pro Pro Ser Thr Ala Pro Ser Gly Pro Gly Ser Val Gin Lys 590 595 600 605 TAC ATC GTG GTC TCA CTT CCC CCA ACA GGG GAG GGC AAA GGA GGC CCC 2834 Tyr He Val Val Ser Leu Pro Pro Thr Gly Glu Gly Lys Gly Gly Pro 610 615 620 ACC TCC CAT CCT TCT CCA GTT CCT CCC CCG GCA TCG TCC CCG TCC CCA 2882 Thr Ser His Pro Ser Pro Val Pro Pro Pro Ala Ser Ser Pro Ser Pro 130 625 630 635 CTC AGC GGC AGT CGG GTT TGT GGG GGG AAG CAG GAG GCT GGG GAC AGT 2930 Leu Ser Gly Ser Arg Val Cys Gly Gly Lys Gin Glu Ala Gly Asp Ser 640 645 650 CCC CCT CCA GCT CCA GGG ACT CCA AAA GCC AAT GGC TCC CAG CCC AAC 2978 Pro Pro Pro Ala Pro Gly Thr Pro Lys Ala Asn Gly Ser Gin Pro Asn 655 660 665 TGC GGC TCC CCT CAG CCT GCT CCG TGATGCTCCA CCTGCCAGCC CCCGGATTCC 3032 Cys Gly Ser Pro Gin Pro Ala Pro 670 675 CACACATGCA GACATGTACA CACGTGCACG TACACACATG CATGCTCGCT AAGCGGAAGG 3092 AAGTTGTAGA TTGCTTCCTT CATGTCACTT TCTTTTTAGA TATTGTACAG CCAGTTTCTC 3152 AGAATAAAAG TTTGGTTTGT AAAAAAAAAA 3182 (2) INFORMATION FOR SEQ ID NO: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 677 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: Met Ala Glu Glu Lys Lys Leu Lys Leu Ser Asn Thr Val Leu Pro Ser T31 10 15 Glu Ser Met Lys Val Val Ala Glu Ser Met Gly He Ala Gin He Gin 20 25 30 Glu Glu Thr Cys Gin Leu Leu Thr Asp Glu Val Ser Tyr Arg He Lys 35 40 45 Glu He Ala Gin Asp Ala Leu Lys Phe Met His Met Gly Lys Arg Gin 50 55 60 Lys Leu Thr Thr Ser Asp He Asp Tyr Ala Leu Lys Leu Lys Asn Val 65 70 75 80 Glu Pro Leu Tyr Gly Phe His Ala Gin Asp Phe He Pro Phe Arg Phe 85 90 95 Ala Ser Gly Gly Gly Arg Glu Leu Tyr Phe Tyr Glu Glu Lys Glu Val 100 105 110 Asp Leu Ser Asp He He Asn Thr Pro Leu Pro Arg Val Pro Leu Asp 115 120 125 Val Cys Leu Lys Ala His Trp Leu Ser He Glu Gly Cys Gin Pro Ala 130 135 140 He Pro Glu Asn Pro Pro Pro Ala Pro Lys Glu Gin Gin Lys Ala Glu 145 150 155 160 Ala Thr Glu Pro Leu Lys Ser Ala Lys Pro Gly Gin Glu Glu Asp Gly 165 170 175 132 Pro Leu Lys Gly Lys Gly Gin Gly Ala Thr Thr Ala Asp Gly Lys Gly 180 185 190 Lys Glu Lys Lys Ala Pro Pro Leu Leu Glu Gly Ala Pro Leu Arg Leu 195 200 205 Lys Pro Arg Ser He His Glu Leu Ser Val Glu Gin Gin Leu Tyr Tyr 210 215 220 Lys Glu He Thr Glu Ala Cys Val Gly Ser Cys Glu Ala Lys Arg Ala 225 230 235 240 Glu Ala Leu Gin Ser He Ala Thr Asp Pro Gly Leu Tyr Gin Met Leu 245 250 255 Pro Arg Phe Ser Thr Phe He Ser Glu Gly Val Arg Val Asn Val Val 260 265 270 Gin Asn Asn Leu Ala Leu Leu He Tyr Leu Met Arg Met Val Lys Ala 275 280 285 Leu Met Asp Asn Pro Thr Leu Tyr Leu Glu Lys Tyr Val His Glu Leu 290 295 300 He Pro Ala Val Met Thr Cys He Val Ser Arg Gin Leu Cys Leu Arg 305 310 315 320 Pro Asp Val Asp Asn His Trp Ala Leu Arg Asp Phe Ala Ala Arg Leu 325 330 335 Val Ala Gin He Cys Lys His Phe Ser Thr Thr Thr Asn Asn He Gin 340 345 350 133 Ser Arg He Thr Lys Thr Phe Thr Lys Ser Trp Val Asp Glu Lys Thr 355 360 365 Pro Trp Thr Thr Arg Tyr Gly Ser He Ala Gly Leu Ala Glu Leu Gly 370 375 380 His Asp Val He Lys Thr Leu He Leu Pro Arg Leu Gin Thr Phe Thr 385 390 395 400 Lys Ser Trp Val Asp Glu Lys Thr Pro Trp Thr Thr Arg Tyr Gly Ser 405 410 415 Arg He Gly Ala Asp His Val Gin Ser Leu Leu Leu Lys His Cys Ala 420 425 430 Pro Val Leu Ala Lys Leu Arg Pro Pro Pro Asp Asn Gin Asp Ala Tyr 435 440 445 Arg Ala Glu Phe Gly Ser Leu Gly Pro Leu Leu Cys Ser Gin Val Val 450 455 460 Lys Ala Arg Ala Gin Ala Ala Leu Gin Ala Gin Gin Val Asn Arg Thr 465 470 475 480 Thr Leu Thr He Thr Gin Pro Arg Pro Thr Leu Thr Leu Ser Gin Ala 485 490 495 Pro Gin Pro Gly Pro Arg Thr Pro Gly Leu Leu Lys Val Pro Gly Ser 500 505 510 He Ala Leu Pro Val Gin Thr Leu Val Ser Ala Arg Ala Ala Ala Pro 515 520 525 t34 Pro Gin Pro Ser Pro Pro Pro Thr Lys Phe He Val Met Ser Ser Ser 530 535 540 Ser Ser Ala Pro Ser Thr Gin Gin Val Leu Ser Leu Ser Thr Ser Ala 545 550 555 560 Pro Gly Ser Gly Ser Thr Thr Thr Ser Pro Val Thr Thr Thr Val Pro 565 570 575 Ser Val Gin Pro He Val Lys Leu Val Ser Thr Ala Thr Thr Ala Pro 580 585 590 Pro Ser Thr Ala Pro Ser Gly Pro Gly Ser Val Gin Lys Tyr He Val 595 600 605 Val Ser Leu Pro Pro Thr Gly Glu Gly Lys Gly Gly Pro Thr Ser His 610 615 620 Pro Ser Pro Val Pro Pro Pro Ala Ser Ser Pro Ser Pro Leu Ser Gly 625 630 635 640 Ser Arg Val Cys Gly Gly Lys Gin Glu Ala Gly Asp Ser Pro Pro Pro 645 650 655 Ala Pro Gly Thr Pro Lys Ala Asn Gly Ser Gin Pro Asn Cys Gly Ser 660 665 670 Pro Gin Pro Ala Pro 675 135 dTAFII250 amino acid sequence MGPGCDLLLRTAATITAAAIMSDTDSDEDSAGGGPFSLAGFLFGNINGAGQLEGESV LDDEC_O HLAGLGALGLGSLITELTAN__I_LTGTDGALVNDEGWVRSTEDAVDYSDIN EVAEDESRRY(^TMGSI_QPLCΗSDYDEDDYDADCEDroCKLMPPPPPPPGPMKKDKD QDSITGEKVDFSSSSDSESEMGPQEATQAESEDGKLTLPLAGIMQHDATKLLPSVTEL _ΨEFT^GK\ _RFLRI_FGPG___WPSVWRSARRKRKKXI RELIQE QKSLWNYDYAPPPPPEQCLSDDEITMMAPVESKFSQSTGDIDKVTDTKPRVAEWRY GPARLWYDMLGWEDGSGFDYGFTOJUCTEHEPVIKSRMIEE^ N_^MVTT_)LHWEDDIIWDGEDVKHKGTK QRASLAGWLPSSMT1WAMAYNVQQGF AATLDDDKPWYSIFPIDNEDLVYGRWEDNΠWDAQA PRLI_EPPVLTLDPNDENLI I_EIPDE__EEAT^NSPSKESKKESSLKKSRILLGKTGVIKEEP(^NMSQPEVKDPWNLSN DEYYYPKQQGLRGTFGGNΠQHSIPAVELRQPFFPTHMGPIKLRQFHRPPLKKYSFGA I^QPGPHSVQPIXKHIKK_ AKMREQERQASGGGEMFFMRTPQDLTGKDGDLILAEY_^ EENGPLMMQVGMAT IK ΥKRKPGKDPGAPDCKYGETVYC ^PR .GSLW^ QAFENNLFRAPIYLHKMPEΠ)FLI_RTRQGYYIRELVDIFVVGQQCPLFEVPGPNSKR ANTFFLRDFLQVHYRLFWKSKDRPRR MEDIKKAF SHSESSIRKRLKLCADFK^ MDSNWWVLKSDFRLPTEEEIRAMVSPEQCCAYYSMIAAEQRLKDAGYGEKSFFAPE EENEEDFQMKMDEVRTAPWNT AHAAMKGKCLLEVTGVADPTGCGEGFSYVKI PNKPTQQKDDKEPQPVKKWTGTDADLRRLSLKNAKQLLRIO^GVPEEEIKKLSRWEV ΩVVRTMSTEQARSGEGPMSKFARGSRFSVAEHQERYKEECQRIFDLQM VL_SSTEVL STDTDSSSAEDSDFEEMGKNIENMLQNKKTSSQLSREREEQERKELQRMLLAAGSAAS GNNHRDDDTASVTSI^SSATGRCLKIYRTFRDEEGKEYVRCΕTWKPA\^AYVR TΠΦEEFIRKFAIJ EQHREEMRKERRRIQEQL^ PDLKLKCGACGAIGHMRTN FCPLYYQTNAPPSNPVAMTEEQEEE1.EKTVIHNDNEE LIKVEGTKIVLGKQLFFISADE\TOKSLVLKFPKQQ SIHRRRTDPMVT SSILESΠNDMRDLPNTYPFHTPVNAKVVKDYYKIITRPMDLQT LREN\ΗKRLYPSREEFREHI_ELIVKNSATYN^^ ARLEKAII^LLDDDDQVAFSFILD VTQKMMAVPDSWPFHHPVNKKFVPDYYKV IVNPMDLEΉRKMSKHKYQSRESFLDDVNLILANSVKYNGPESQYTKTAQEIVNVCY QT TEYDEHLTQLEKDICTAKEAALEEAELESLDPMTPGPYTPQPPDLYDT TSLSMS RDASXTQDESNMSVLDIPSATPEKQVTQEGEDGDGDLADEEEGTVQQPQASVLYEDL IJVISEGEDDEEDAGSDEEGDNPFSAIQL^ESGSDSDVGSGGIRPKQPRMLQENTRMDME NEESMMSYEGIX GEASHGI_EDSMSYGSYEEPDPKSNTQDTSR^SIGGYEVSEEF_EDEEE EEQRSGPSVLSQVHLSEDEEDSEDFHSIAGDSDLDSDE 1 3 6 Sequence Range: 1 to 2214 5 10 15 20 25 30 35 40 45 * * * * AGA GGT GGT GCA GGC GGC GCC CCC GGC GGC GCA GAC CCT GGC GCC AGC Arg Gly Gly Ala Gly Gly Ala Pro Gly Gly Ala Asp Pro Gly Ala Ser> a a a TRANSLATION OF HTAF130 DNA .Al a a a a > 50 55 60 65 70 75 80 85 90 95 * * * * * GGC CCG GCC AGC ACG GCG GCC AGC ATG GTC ATC GGG CCA ACT ATG CAA Gly Pro Ala Ser Thr Ala Ala Ser Met Val He Gly Pro Thr Met Gln> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 100 105 110 115 120 125 130 135 140 * * ★ * * GGG CGC TGC CCA GCC CGG CCG CCG TCC CGC CGC CCG CCC CCG GGA CCC Gly Arg Cys Pro Ala Arg Pro Pro Ser Arg Arg Pro Pro Pro Gly Pro> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 145 150 155 160 165 170 175 180 185 190 * * * * * CCA CCG GGC TGC CCA AAA GGC GCG GCC GGC GCA GTG ACC CAG AGC CTG Pro Pro Gly Cys Pro Lys Gly Ala Ala Gly Ala Val Thr Gin Ser Leu> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 195 200 205 210 215 220 225 230 235 240 * * * * * TCC CGG ACG CCC ACG GCC ACC ACC AGC GGG ATT CGG GCC ACC CTG ACG Ser Arg Thr Pro Thr Ala Thr Thr Ser Gly He Arg Ala Thr Leu Thr> a a a TRANSLATION OF HTAF130 DNA .Al a a a a > 245 250 255 260 265 270 275 280 285 * * * * CCC ACC GTG CTG GCC CCC CGC TTG CCG CAG CCG CCT CAG AAC CCG ACC Pro Thr Val Leu Ala Pro Arg Leu Pro Gin Pro Pro Gin Asn Pro Thr> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 290 295 300 305 310 315 320 325 330 335 * * * * * AAC ATC CAG AAC TTC CAG CTG CCC CCA GGA ATG GTC CTC GTC CGA AGT Asn He Gin Asn Phe Gin Leu Pro Pro Gly Met Val Leu Val Arg Ser> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 340 345 350 355 360 365 370 375 380 * * * * * GAG AAT GGG CAG TTG TTA ATG ATT CCT CAG CAG GCC TTG GCC CAG ATG Glu Asn Gly Gin Leu Leu Met He Pro Gin Gin Ala Leu Ala Gin Met> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 385 390 395 400 405 410 415 420 425 430 * * * * * CAG GCG CAG GCC CAT GCC CAG CCT CAG ACC ACC ATG GCG CCT CGC CCT Gin Ala Gin Ala His Ala Gin Pro Gin Thr Thr Met Ala Pro Arg Pro> a a a TRANSLATION OF HTAF130 DNA [A]_a a __a a > 435 440 ' 445 450 455 460 465 470 475 480 * * * * * GCC ACC CCC ACA AGT GCC CCT CCC GTC CAG ATC TCC ACC GTA CAG GCA Ala Thr Pro Thr Ser Ala Pro Pro Val Gin He Ser Thr Val Gin Ala> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1 3 7 485 490 495 500 505 510 515 520 525 * * * * CCT GGA ACA CCT ATC ATT GCA CGG CAG GTG ACC CCA ACT ACC ATA ATT Pro Gly Thr Pro He He Ala Arg Gin Val Thr Pro Thr Thr He He> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 530 535 540 545 550 555 560 565 570 575 * * * * * AAG CAA GTG TCT CAG GCC CAG ACA ACG GTG CAG CCC AGT GCA ACC CTG Lys Gin Val Ser Gin Ala Gin Thr Thr Val Gin Pro Ser Ala Thr Leu> a a a TRANSLATION OF HTAF130 DNA [A}_a a a a > 580 585 590 595 600 605 610 615 620 * * * * * CAG CGC TCG CCC GGC GTC CAG CCT CAG CTC GTT CTG GGT GGC GCT GCC Gin Arg Ser Pro Gly Val Gin Pro Gin Leu Val Leu Gly Gly Ala Ala> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 625 630 635 640 645 650 655 660 665 670 * * * * * CAG ACG GCT TCA CTT GGG ACG GCG ACG GCT GTT CAG ACG GGG ACT CCT Gin Thr Ala Ser Leu Gly Thr Ala Thr Ala Val Gin Thr Gly Thr Pro> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 675 680 685 690 695 700 705 710 715 720 * * * * ★ CAG CGC ACG GTA CCA GGG GCG ACC ACC ACT TCC TCA GCT GCC ACG GAA Gin Arg Thr Val Pro Gly Ala Thr Thr Thr Ser Ser Ala Ala Thr Glu> a a a TRANSLATION OF HTAF130 DNA .Al a a a a > 725 730 735 740 745 750 755 760 765 * * * * ACT ATG GAA AAC GTG AAG AAA TGT AAA AAT TTC CTA TCT ACG TTA ATA Thr Met Glu Asn Val Lys Lys Cys Lys Asn Phe Leu Ser Thr Leu He> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 770 775 780 785 790 795 800 805 810 815 * * * * * AAA CTG GCT TCA TCT GGC AAG CAG TCT ACA GAG ACA GCA GCT AAT GTG Lys Leu Ala Ser Ser Gly Lys Gin Ser Thr Glu Thr Ala Ala Asn Val> a a a TRANSLATION OF HTAF130 DNA [Al a a a a > 820 825 830 835 840 845 850 855 860 * * * * * AAA GAG CTC GTG CAG AAT TTA CTG GAT GGA AAA ATA GAA GCA GAA GAT Lys Glu Leu Val Gin Asn Leu Leu Asp Gly Lys He Glu Ala Glu Asp> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 865 870 875 880 885 890 895 900 905 910 * * * * * TTC ACA AGC AGG TTA TAC CGA GAA CTT AAT TCT TCA CCT CAA CCT TAC Phe Thr Ser Arg Leu Tyr Arg Glu Leu Asn Ser Ser Pro Gin Pro Tyr > a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 915 920 925 930 935 940 945 950 955 960 * * * * * CTT GTG CCT TTC CTG AAG AGG AGC TTA CCC GCC TTG AGA CAG CTG ACC Leu Val Pro Phe Leu Lys Arg Ser Leu Pro Ala Leu Arg Gin Leu Thr > a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 965 970 975 980 985 990 995 1000 1005 * * * * 1 3 8 CCC GAC TCC GCG GCC TTC ATC CAG CAG AGC CAG CAG CAG CCG CCA CCG Pro Asp Ser Ala Ala Phe He Gin Gin Ser Gin Gin Gin Pro Pro Pro> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1010 1015 1020 1025 1030 1035 1040 1045 1050 1055 * * * * * CCC ACC TCG CAG GCC ACC ACT GCG CTC ACG GCC GTG GTG CTG AGT AGC Pro Thr Ser Gin Ala Thr Thr Ala Leu Thr Ala Val Val Leu Ser Ser> a a a TRANSLATION OF HTAF130 DNA [A__a a a a > 1060 1065 1070 1075 1080 1085 1090 1095 1100 * * * * * TCG GTC CAG CGC ACG GCC GGG AAG ACG GCG GCC ACC GTG ACC AGT GCC Ser Val Gin Arg Thr Ala Gly Lys Thr Ala Ala Thr Val Thr Ser Ala> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1105 1110 1115 1120 1125 1130 1135 1140 1145 1150 * * * * * CTC CAG CCC CCT GTG CTC AGC CTC ACG CAG CCC ACG CAG GTC GGC GTC Leu Gin Pro Pro Val Leu Ser Leu Thr Gin Pro Thr Gin Val Gly Val> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1155 1160 1165 1170 1175 1180 1185 1190 1195 1200 * * * * * GGC AAG CAG GGG CAA CCC ACA CCG CTG GTC ATC CAG CAG CCT CCG AAG Gly Lys Gin Gly Gin Pro Thr Pro Leu Val He Gin Gin Pro Pro Lys> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1205 1210 1215 1220 1225 1230 1235 1240 1245 * * * * CCA GGA GCC CTG ATC CGG CCC CCG CAG GTG ACG TTG ACG CAG ACA CCC Pro Gly Ala Leu He Arg Pro Pro Gin Val Thr Leu Thr Gin Thr Pro> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 1250 1255 1260 1265 1270 1275 1280 1285 1290 1295 * * * * * ATG GTC GCC CTG CGG CAG CCT CAC AAC CGG ATC ATG CTC ACC ACG CCT Met Val Ala Leu Arg Gin Pro His Asn Arg He Met Leu Thr Thr Pro> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1300 1305 1310 1315 1320 1325 1330 1335 1340 * * * * * CAG CAG ATC CAG CTG AAC CCA CTG CAG CCA GTC CCT GTG GTG AAA CCC Gin Gin He Gin Leu Asn Pro Leu Gin Pro Val Pro Val Val Lys Pro> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 1345 1350 1355 1360 1365 1370 1375 1380 1385 1390 * * _. * * * GCC GTG TTA CCT GGA ACC AAA GCC CTT TCT GCT GTC TCG GCA CAA GCA Ala Val Leu Pro Gly Thr Lys Ala Leu Ser Ala Val Ser Ala Gin Ala> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1395 1400 1405 1410 1415 1420 1425 1430 1435 1440 * * * * * GCT GCT GCA CAG AAA AAT AAA CTC AAG GAG CCT GGG GGA GGT TCG TTT Ala Ala Ala Gin Lys Asn Lys Leu Lys Glu Pro Gly Gly Gly Ser Phe> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1445 1450 1455 1460 1465 1470 1475 1480 1485 * * * * CGG GAC GAT GAT GAC ATT AAT GAT GTT GCA TCG ATG GCT GGA GTA AAC Arg Asp Asp Asp Asp He Asn Asp Val Ala Ser Met Ala Gly Val Asn> 1 3 9 . TRANSLATION OF HTAF130 DNA [A] _a_ 1490 1495 1500 1505 1510 1515 1520 1525 1530 1535 * * * * * TTG TCA GAA GAA AGT GCA AGA ATA TTA GCC ACG AAC TCT GAA TTG GTG Leu Ser Glu Glu Ser Ala Arg He Leu Ala Thr Asn Ser Glu Leu Val> a a a TRANSLATION OF HTAF130 DNA _A]_a a a a > 1540 1545 1550 1555 1560 1565 1570 1575 1580 * * * * * GGC ACG CTA ACG CGG TCC TGT AAA GAT GAA ACC TTC CTC CTC CAA GCG Gly Thr Leu Thr Arg Ser Cys Lys Asp Glu Thr Phe Leu Leu Gin Ala> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1585 1590 1595 1600 1605 1610 1615 1620 1625 1630 * * * * * CCT TTG CAG AGA AGA ATA TTA GAA ATA GGT AAA AAA CAT GGT ATA ACG Pro Leu Gin Arg Arg He Leu Glu He Gly Lys Lys His Gly He Thr> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1635 1640 1645 1650 1655 1660 1665 1670 1675 1680 * * * * * GAA TTA CAT CCA GAT GTA GTA AGT TAT GTA TCA CAT GCC ACG CAA CAA Glu Leu His Pro Asp Val Val Ser Tr Val Ser His Ala Thr Gin Gln> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1685 1690 1695 1700 1705 1710 1715 1720 1725 * * * * AGG CTA CAG AAT CTT GTA GAG AAA ATA TCA GAA ACA GCT CAG CAG AAG Arg Leu Gin Asn Leu Val Glu Lys He Ser Glu Thr Ala Gin Gin Lys> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1730 1735 1740 1745 1750 1755 1760 1765 1770 1775 * * * * * AAC TTT TCT TAC AAG GAT GAC GAC AGA TAT GAG CAG GCG AGT GAC GTC Asn Phe Ser Tyr Lys Asp Asp Asp Arg Tyr Glu Gin Ala Ser Asp Val> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1780 1785 1790 1795 1800 1805 1810 1815 1820 * * * * * CGG GCA CAG CTC AAG TTT TTT GAA CAG CTT GAT CAA ATC GAA AAG CAG Arg Ala Gin Leu Lys Phe Phe Glu Gin Leu Asp Gin He Glu Lys Gln> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 1825 1830 1835 1840 1845 1850 1855 1860 1865 1870 * * * * * AGG AAG GAT GAG CAG GAG CGG GAG ATC CTG ATG AGG GCA GCA AAG TCT Arg Lys Asp Glu Gin Glu Arg Glu He Leu Met Arg Ala Ala Lys Ser> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 1875 1880 1885 1890 1895 1900 1905 1910 1915 1920 * * * * * CGG TCA AGA CAA GAA GAT CCA GAA CAG TTA AGG CTG AAA CAG AAG GCA Arg Ser Arg Gin Glu Asp Pro Glu Gin Leu Arg Leu Lys Gin Lys Ala> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1925 1930 1935 1940 1945 1950 1955 1960 1965 * * * * AAG GAG ATG CAG CAA CAG GAA CTG GCA CAA ATG AGA CAG CGG GAC GCC Lys Glu Met Gin Gin Gin Glu Leu Ala Gin Met Arg Gin Arg ASD Ala> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 1 4 0 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 * * * * * AAC CTC ACA GCA CTA GCA GCG ATC GGG CCC AGG AAA AAG AGG AAA GTG Asn Leu Thr Ala Leu Ala Ala He Gly Pro Arg Lys Lys Arg Lys Val> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 2020 2025 2030 2035 2040 2045 2050 2055 2060 * * * * * GAC TGT CCG GGG CCG GGC TCA GGA GCA GAG GGG TCG GGC CCC GGC TCA Asp Cys Pro Gly Pro Gly Ser Gly Ala Glu Gly Ser Gly Pro Gly Ser> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 2065 2070 2075 2080 2085 2090 2095 2100 2105 2110 * * * * * GTG GTC CCA GGC AGC TCG GGT GTC GGA ACC CCC AGA CAG TTC ACG CGA Val Val Pro Gly Ser Ser Gly Val Gly Thr Pro Arg Gin Phe Thr Arg> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 2115 2120 2125 2130 2135 2140 2145 2150 2155 2160 * * * * * CAA AGA ATC ACG CGG GTC AAC CTC AGG GAC CTC ATA TTT TGT TTA GAA Gin Arg He Thr Arg Val Asn Leu Arg Asp Leu He Phe Cys Leu Glu> a a a TRANSLATION OF HTAF130 DNA [A]_a a a a > 2165 2170 2175 2180 2185 2190 2195 2200 2205 * * * * AAT GAA CGT GAG ACA AGC CAT TCA CTG CTG CTC TAC AAA GCA TTC CTT Asn Glu Arg Glu Thr Ser His Ser Leu Leu Leu Tyr Lys Ala Phe Leu> a a a TRANSLATION OF HTAF130 DNA fAl a a a a > 2210 * AAG TGA Lys ***> a > 1 4 1 5 10 15 20 25 30 35 40 45 50 * * * * * RGGAGGAPGG ADPGASGPAS TAASMVIGPT MQGRCPARPP SRRPPPGPPP 55 60 65 70 75 80 85 90 95 100 * * * * * GCPKGAAGAV TQSLSRTPTA TTSGIRATLT PTVLAPRLPQ PPQNPTNIQN 105 110 115 120 125 130 135 140 145 150 * * * * * FQLPPGMVLV RSENGQLLMI PQQALAQMQA QAHAQPQTTM APRPATPTSA 155 160 165 170 175 180 185 190 195 200 * * * * * PPVQISTVQA PGTPIIARQV TPTTIIKQVS QAQTTVQPSA TLQRSPGVQP 205 210 215 220 225 230 235 240 245 250 * * * * * QLVLGGAAQT ASLGTATAVQ TGTPQRTVPG ATTTSSAATE TMENVKKCKN 255 260 265 270 275 280 285 290 295 300 FLSTLIKLAS SGKQSTETAA NVKELVQNLL DGKIEAEDFT SRLYRELNSS 305 310 315 320 325 330 335 340 345 350 * * * * * PQPYLVPFLK RSLPALRQLT PDSAAFIQQS QQQPPPPTSQ ATTALTAWL 355 360 365 370 375 380 385 390 395 400 * * * * * SSSVQRTAGK TAATVTSALQ PPVLSLTQPT QVGVGKQGQP TPLVIQQPPK 405 410 415 420 425 430 435 440 445 450 * * * * * PGALIRPPQV TLTQTPMVAL RQPHNRIMLT TPQQIQLNPL QPVPWKPAV 455 460 465 470 475 480 485 490 495 500 * * * * * LPGTKALSAV SAQAAAAQKN KLKEPGGGSF RDDDDINDVA SMAGVNLSEE 505 510 515 520 525 530 535 540 545 550 * * * * * SARILATNSE LVGTLTRSCK DETFLLQAPL QRRILEIGKK HGITELHPDV 555 560 565 570 575 580 585 590 595 600 * * * * * VSYVSHATQQ RLQNLVEKIS ETAQQKNFSY KDDDRYEQAS DVRAQLKFFE 605 610 615 620 625 630 635 640 645 650 * * * * * QLDQIEKQRK DEQEREILMR AAKSRSRQED PEQLRLKQKA -KEMQQQELAQ 655 660 665 670 675 680 685 690 695 700 * * * * * MRQRDANLTA LAAIGPRKKR KVDCPGPGSG AEGSGPGSW PGSSGVGTPR 705 710 715 720 725 730 735 * * * QFTRQRITRV NLRDLIFCLE NERETSHΞLL LYKAFLK* 142 Sequence Range: 1 to 2152 5 10 15 20 25 30 35 40 45 * * * * CTA CTG GCC GTG CTG CAG TTC CTA CGG CAG AGC AAA CTC CGC GAG GCC Leu Leu Ala Val Leu Gin Phe Leu Arg Gin Ser Lys Leu Arg Glu Ala> a a_ ^ a___TRANSLATION OF HTAF100 DNA [A]_a a a a > 50 55 60 65 70 75 80 85 90 95 * * * * * GAA GAG GCG CTG CGC CGT GAG GCC GGG CTG CTG GAG GAG GCA GTG GCG Glu Glu Ala Leu Arg Arg Glu Ala Gly Leu Leu Glu Glu Ala Val Ala> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 100 105 110 115 120 125 130 135 140 * * * * * GGC TCC GGA GCC CCG GGA GAG GTG GAC AGC GCC GGC GCT GAG GTG ACC Gly Ser Gly Ala Pro Gly Glu Val Asp Ser Ala Gly Ala Glu Val Thr> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 145 150 155 160 165 170 175 180 185 190 * * * * * AGC GCG CTT CTC AGC CGG GTG ACC GCC TCG GCC CCT GGC CCT GCG GCC Ser Ala Leu Leu Ser Arg Val Thr Ala Ser Ala Pro Gly Pro Ala Ala> a a__a__TRANSLATION OF HTAF100 DNA [A]_a a a a > 195 200 205 210 215 220 225 230 235 240 * * * * * CCC GAC CCT CCG GGC ACT GGC GCT TCG GGG GCC ACG GTC GTC TCA GGT Pro Asp Pro Pro Gly Thr Gly Ala Ser Gly Ala Thr Val Val Ser Gly> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 245 250 255 260 265 270 275 280 285 * * * * TCA GCC TCA GGT CCT GCG GCT CCG GGT AAA GTT GGA AGT GTT GCT GTG Ser Ala Ser Gly Pro Ala Ala Pro Gly Lys Val Gly Ser Val Ala Val> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 290 295 300 305 310 315 320 325 330 335 * * * * * GAA GAC CAG CCA GAT GTC AGT GCC GTG TTG TCA GCC TAC AAC CAA CAA Glu Asp Gin Pro Asp Val Ser Ala Val Leu Ser Ala yr Asn Gin Gln> a a a TRANSLATION OF HTAF100 DNA [A__a a a a > 340 345 350 355 360 365 370 375 380 * * * * * GGA GAT CCC ACA ATG TAT GAA GAA TAC TAT AGT GGA CTG AAA CAC TTC Gly Asp Pro Thr Met Tyr Glu Glu Tyr Tyr Ser Gly Leu Lys His Phe> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 385 390 395 400 405 410 415 420 425 430 * * * * * ATT GAA TGT TCC CTG GAC TGC CAT CGG GCA GAG TTG TCC CAA CTT TTT He Glu Cys Ser Leu Asp Cys His Arg Ala Glu Leu Ser Gin Leu Phe> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 435 440 445 450 455 460 465 470 475 480 * * * * * TAT CCT CTG TTT GTG CAC ATG TAC TTG GAG CTA GTC TAC AAT CAA CAT Tyr Pro Leu Phe Val His Met Tyr Leu Glu Leu Val Tyr Asn Gin His > a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1 4 3 485 490 495 500 505 510 515 520 525 * * * * GAG AAT GAA GCA AAG TCA TTC TTT GAG AAG TTC CAT GGA GAT CAG GAA Glu Asn Glu Ala Lys Ser Phe Phe Glu Lys Phe His Gly Asp Gin Glu> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 530 535 540 545 550 555 560 565 570 575 * * * * * TGT TAT TAC CAG GAT GAC CTA CGA GTA TTA TCT AGT CTT ACC AAA AAG Cys Tyr Tyr Gin Asp Asp Leu Arg Val Leu Ser Ser Leu Thr Lys Lys> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 580 585 590 595 600 605 610 615 620 * * * * * GAA CAC ATG AAA GGG AAT GAG ACC ATG TTG GAT TTT CGA ACA AGT AAA Glu His Met Lys Gly Asn Glu Thr Met Leu Asp Phe Arg Thr Ser Lys> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 625 630 635 640 645 650 655 660 665 670 * * * * * TTT GTT CTG CGT ATT TCC CGT GAC TCG TAC CAA CTC TTG AAG AGG CAT Phe Val Leu Arg He Ser Arg Asp Ser Tyr Gin Leu Leu Lys Arg His> a a a TRANSLATION OF HTAF100 DNA [A__a a a a > 675 680 685 690 695 700 705 710 715 720 * * * * * CTT CAG GAG AAA CAG AAC AAT CAG ATA TGG AAC ATA GTT CAG GAG CAC Leu Gin Glu Lys Gin Asn Asn Gin He Trp Asn He Val Gin Glu His> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 725 730 735 740 745 750 755 760 765 * * * * CTC TAC ATT GAC ATC TTT GAT GGG ATG CCG CGT AGT AAG CAA CAG ATA Leu Tyr He Asp He Phe Asp Gly Met Pro Arg Ser Lys Gin Gin He> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 770 775 780 785 790 795 800 805 810 815 * ★ * * * GAT GCG ATG GTG GGA AGT TTG GCA GGA GAG GCT AAA CGA GAG GCA AAC Asp Ala Met Val Gly Ser Leu Ala Gly Glu Ala Lys Arg Glu Ala Asn> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 820 825 830 835 840 845 850 855 860 * * * * * AAA TCA AAG GTA TTT TTT GGT TTA TTA AAA GAA CCA GAA ATT GAG GTA Lys Ser Lys Val Phe Phe Gly Leu Leu Lys Glu Pro Glu He Glu Val> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 865 870 875 880 885 890 895 900 905 910 * * * * * CCT TTG GAT GAC GAG GAT GAA GAG GGA GAA AAT GAA GAA GGA AAA CCT Pro Leu Asp Asp Glu Asp Glu Glu Gly Glu Asn Glu Glu Gly Lys Pro a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 915 920 925 930 935 940 945 950 955 960 * * * * * AAA AAG AAG AAG CCT AAA AAA GAT AGT ATT GGA TCC AAA AGC AAA AAA Lys Lys Lys Lys Pro Lys Lys Asp Ser He Gly Ser Lys Ser Lys Lys> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 965 970 975 980 985 990 995 1000 1005 1 4 4 CAA GAT CCC AAT GCT CCA CCT CAG AAC AGA ATC CCT CTT CCT GAG TTG Gin Asp Pro Asn Ala Pro Pro Gin Asn Arg He Pro Leu Pro Glu Leu> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1010 1015 1020 1025 1030 1035 1040 1045 1050 1055 * * * * * AAA GAT TCA GAT AAG TTG GAT AAG ATA ATG AAT ATG AAA GAA ACC ACC Lys Asp Ser Asp Lys Leu Asp Lys He Met Asn Met Lys Glu Thr Thr> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1060 1065 1070 1075 1080 1085 1090 1095 1100 * * * * * AAA CGA GTA CGC CTT GGG CCG GAC TGC TTA CCC TCC ATT TGT TTC TAT Lys Arg Val Arg Leu Gly Pro Asp Cys Leu Pro Ser He Cys Phe Tyr> a a a TRANSLATION OF HTAF100 DNA [A__a a a a > 1105 1110 1115 1120 1125 1130 1135 1140 1145 1150 * * * * * ACA TTT CTC AAT GCT TAC CAG GGT CTC ACT GCA GTG GAT GTC ACT GAT Thr Phe Leu Asn Ala Tyr Gin Gly Leu Thr Ala Val Asp Val Thr Asp> a a__a__TRANSLATION OF HTAF100 DNA [A]_a a a a > 1155 1160 1165 1170 1175 1180 1185 1190 1195 1200 ★ * * * * GAT TCT AGT CTG ATT GCT GGA GGT TTT GCA GAT TCA ACT GTC AGA GTG Asp Ser Ser Leu He Ala Gly Gly Phe Ala Asp Ser Thr Val Arg Val> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1205 1210 1215 1220 1225 1230 1235 1240 1245 * * * * TGG TCG GTA ACA CCC AAA AAG CTT CGT AGT GTC AAA CAA GCA TCA GAT Trp Ser Val Thr Pro Lys Lys Leu Arg Ser Val Lys Gin Ala Ser Asp> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1250 1255 1260 1265 1270 1275 1280 1285 1290 1295 * * * * * CTT AGT CTT ATA GAC AAA GAA TCA GAT GAT GTC TTA GAA AGA ATC ATG Leu Ser Leu He Asp Lys Glu Ser Asp Asp Val Leu Glu Arg He Met> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1300 1305 1310 1315 1320 1325 1330 1335 1340 * * * * * GAT GAG AAA ACA GCA AGT GAG TTG AAG ATT TTG TAT GGT CAC AGT GGG Asp Glu Lys Thr Ala Ser Glu Leu Lys He Leu Tyr Gly His Ser Gly> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1345 1350 1355 1360 1365 1370 1375 1380 1385 1390 * * * * * CCT GTC TAC GGA GCC AGC TTC AGT CCG GAT AGG AAC TAT CTG CTT TCC Pro Val Tyr Gly Ala Ser Phe Ser Pro Asp Arg Asn Tyr Leu Leu Ser> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1395 1400 1405 1410 1415 1420 1425 1430 1435 1440 * * * * * TCT TCA GAG GAC GGA ACT GTT AGA TTG TGG AGC CTT CAA ACA TTT ACT Ser Ser Glu Asp Gly Thr Val Arg Leu Trp Ser Leu Gin Thr Phe Thr> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1445 1450 1455 1460 1465 1470 1475 1480 1485 * * * * TGT TTG GTG GGA TAT AAA GGA CAC AAC TAT CCA GTA TGG GAC ACA CAA Cys Leu Val Gly Ty Lys Gly His Asn Tyr Pro Val Trp Asp Thr Gln> 1 4 5 . TRANSLATION OF HTAF100 DNA [A]_a_ 1490 1495 1500 1505 1510 1515 1520 1525 1530 1535 * * * * * TTT TCN CCA TAT GGA TAT TAT TTT GTG TCA GGG GGC CAT GAC CGA GTA Phe Ser Pro Tyr Gly Tyr Tyr Phe Val Ser Gly Gly His Asp Arg Val> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1540 1545 1550 1555 1560 1565 1570 1575 1580 * * * * * GCT CGG CTC TGG GCT ACA GAC CAC TAT CAG CCT TTA AGA ATA TTT GCC Ala Arg Leu Trp Ala Thr Asp His Tyr Gin Pro Leu Arg He Phe Ala> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1585 1590 1595 1600 1605 1610 1615 1620 1625 1630 * * * * * GGC CAT CTT GCT GAT GTG AAT TGT ACC AGA TTC CAT CCA AAT TCT AAT Gly His Leu Ala Asp Val Asn Cys Thr Arg Phe His Pro Asn Ser Asn> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1635 1640 1645 1650 1655 1660 1665 1670 1675 1680 * * * * * TAT GTT GCT ACG GGC TCT GCA GAC AGA ACT GTG CGG CTC TGG GAC GTC Tyr Val Ala Thr Gly Ser Ala Asp Arg Thr Val Arg Leu Trp Asp Val> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1685 1690 1695 1700 1705 1710 1715 1720 1725 * * * * CTG AAT GGT AAC TGT GTA AGG ATC TTC ACT GGA CAC AAG GGA CCA ATT Leu Asn Gly Asn Cys Val Arg He Phe Thr Gly His Lys Gly Pro He> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1730 1735 1740 1745 1750 1755 1760 1765 1770 1775 * * * * * CAT TCC TTG ACA TTT TCT CCC AAT GGG AGA TTC CTG GCT ACA GGA GCA His Ser Leu Thr Phe Ser Pro Asn Gly Arg Phe Leu Ala Thr Gly Ala> a a a TRANSLATION OF HTAF100 DNA [A__a a a a > 1780 1785 1790 1795 1800 1805 1810 1815 1820 * * * * * ACA GAT GGC AGA GTG CTT CTT TGG GAT ATT GGA CAT GGT TTG ATG GTT Thr Asp Gly Arg Val Leu Leu Trp Asp He Gly His Gly Leu Met Val> a a a TRANSLATION OF HTAF100 DNA fAl a a a a > 1825 1830 1835 1840 1845 1850 1855 1860 1865 1870 * * * * * GGA GAA TTA AAA GGC CAC ACT GAT ACA GTC TGT TCA CTT AGG TTT AGT Gly Glu Leu Lys Gly His Thr Asp Thr Val Cys Ser Leu Arg Phe Ser> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1875 1880 1885 1890 1895 1900 1905 1910 1915 1920 * * * * * AGA GAT GGT GAA ATT TTG GCA TCA GGT TCA ATG GAT AAT ACA GTT CGA Arg Asp Gly Glu He Leu Ala Ser Gly Ser Met Asp Asn Thr Val Arg> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1925 1930 1935 1940 1945 1950 1955 1960 1965 * * * * TTA TGG GAT GCT ATC AAA GCC TTT GAA GAT TTA GAG ACC GAT GAC TTT Leu Trp Asp Ala He Lys Ala Phe Glu Asp Leu Glu Thr Asp Asp Phe> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 1 4 6 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 * * * * * ACT ACA GCC ACT GGG CAT ATA AAT TTA CCT GAG AAT TCA CAG GAG TTA Thr Thr Ala Thr Gly His He Asn Leu Pro Glu Asn Ser Gin Glu Leu> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 2020 2025 2030 2035 2040 2045 2050 2055 2060 * * * * * TTG TTG GGA ACA TAT ATG ACC AAA TCA ACA CCA GTT GTA CAC CTT CAT Leu Leu Gly Thr Tyr Met Thr Lys Ser Thr Pro Val Val His Leu His> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 2065 2070 2075 2080 2085 2090 2095 2100 2105 2110 * * * * * TTT ACT CGA AGA AAC CTG GTT CTA GCT GCA GGA GCT TAT AGT CCA CAA Phe Thr Arg Arg Asn Leu Val Leu Ala Ala Gly Ala Tyr Ser Pro Gln> a a a TRANSLATION OF HTAF100 DNA [A]_a a a a > 2115 2120 2125 2130 2135 2140 2145 2150 * * * * TAA ACCAT CGGTATTAAA GACCAAAAAA AAAAAAAAAA AA *** ,_ 1 4 7 5 10 15 20 25 30 35 40 45 50 * * * * * LLAVLQFLRQ SKLREAEEAL RREAGLLEEA VAGSGAPGEV DSAGAEVTSA 55 60 65 70 75 80 85 90 95 100 * * * * * LLSRVTASAP GPAAPDPPGT GASGATWSG SASGPAAPGK VGSVAVEDQP 105 110 115 120 125 130 135 140 145 150 * * * * * DVSAVLSAYN QQGDPTMYEE YYSGLKHFIE CSLDCHRAEL SQLFYPLFVH 155 160 165 170 175 180 185 190 195 200 * * * * * MYLELVYNQH ENEAKSFFEK FHGDQECYYQ DDLRVLSSLT KKEHMKGNET 205 210 215 220 225 230 235 240 245 250 * * * * * MLDFRTSKFV LRISRDSYQL LKRHLQEKQN NQIWNIVQEH LYIDIFDGMP 255 260 265 270 275 280 285 290 295 300 * * * * * RSKQQIDAMV GSLAGEAKRE ANKSKVFFGL LKEPEIEVPL DDEDEEGENE 305 310 315 320 325 330 335 340 345 350 * * * * * EGKPKKKKPK KDSIGSKSKK QDPNAPPQNR IPLPELKDSD KLDKIMNMKE 355 360 365 370 375 380 385 390 395 400 * * * * * TTKRVRLGPD CLPSICFYTF LNAYQGLTAV DVTDDSSLIA GGFADSTVRV 405 410 415 420 425 430 435 440 445 450 * * * * * WSVTPKKLRS VKQASDLSLI DKESDDVLER IMDEKTASEL KILYGHSGPV 455 460 465 470 475 480 485 490 495 500 * * * * * YGASFSPDRN YLLΞSSEDGT VRLWSLQTFT CLVGYKGHNY PVWDTQFSPY 505 510 515 520 525 530 535 540 545 550 * * * * * GYYFVSGGHD RVARLWATDH YQPLRIFAGH LADVNCTRFH PNSNYVATGS 555 560 565 570 575 580 585 590 595 600 * * * * * ADRTVRLWDV LNGNCVRIFT GHKGPIHSLT FSPNGRFLAT GATDGRVLLW 605 610 615 620 625 630 635 640 645 650 * * * * * DIGHGLMVGE LKGHTDTVCS LRFSRDGEIL ASGSMDNTVR LWDAIKAFED 655 660 665 670 675 680 685 690 695 700 * * * * * LETDDFTTAT GHINLPENSQ ELLLGTYMTK STPWHLHFT RRNLVLAAGA 705 YSPQ* 148 Sequence Range: 1 to 3820 ^^ HD NO ] ^ j 10 20 30 40 50 * * * * * AAT TCC TTT TTT ATA ACA AAC GCA AAT TAG TTA ATT AAA TTC TGG CGC AGA ACC G TTA AGG AAA AAA TAT TGT TTG CGT TTA ATC AAT TAA TTT AAG ACC GCG TCT TGG C 70 80 90 100 110 * * * * * TGA GCG ATG GAA ACG CAA CCT GAG GTG CCC GAG GTG CCG CTG CGA CCG TTT AAA T ACT CGC TAC CTT TGC GTT GGA CTC CAC GGG CTC CAC GGC GAC GCT GGC AAA TTT A M E T Q P E V P E V P L R P F K 130 140 150 160 170 * * * * * CAT CAG GTT GTG AGC CTC ACG GGC ATC AGT TTC GAG CGG AGG AGC ATA ATC GGC G GTA GTC CAA CAC TCG GAG TGC CCG TAG TCA AAG CTC GCC TCC TCG TAT TAG CCG C H Q V V S L T G I S F E R R S I I G 190 200 210 220 230 GAG CTG ACC ATT GTG CCG AAC AGC GAG AAT CTG CGC CTG ATA CGC CTG AAT GCC A CTC GAC TGG TAA CAC GGC TTG TCG CTC TTA GAC GCG GAC TAT GCG GAC TTA CGG T E L T I V P N S E N L R L I R L N A 250 260 270 280 290 * * * * * CTG AGA ATC TAC AGC GTC GTT TTG AAC GAT GTC TGC CAG GCG GAT TTC ACG TAC T GAC TCT TAG ATG TCG CAG CAA AAC TTG CTA CAG ACG GTC CGC CTA AAG TGC ATG A L R I Y S V V L N D V C Q A D F T Y 310 320 330 340 350 * * * * * CCC TTC CAG AAC ATC TGC TAC AAG GAG CCC AAG AGC CGC GCT CTG GAG GTC TAC T GGG AAG GTC TTG TAG ACG ATG TTC CTC GGG TTC TCG GCG CGA GAC CTC CAG ATG A P F Q N I C Y K E P K S R A L E V Y 370 380 390 400 410 * * ★ * * CAT CAT CTG ACC GCC GCC CAG TAC ACC GAT CCC GAT GTG AAC AAC GGC GAA CTG C GTA GTA GAC TGG CGG CGG GTC ATG TGG CTA GGG CTA CAC TTG TTG CCG CTT GAC G H H L T A A Q Y T D P D V N N G E L 430 440 450 460 470 * * ★ * * CAG GTT CCG CCC GAG GGC TAC TCT ATG ATC CAG GAG GGT CAG GGT CTG CGC ATC C GTC CAA GGC GGG CTC CCG ATG AGA TAC TAG GTC CTC CCA GTC CCA GAC GCG TAG G Q V P P E G Y S M I Q E G Q G L R I 490 500 510 520 530 * * * * * GAG TTC TCG TTG GAG AAT CCC AAA TGC GGC GTA CAT TTT GTC ATA CCA CCC GCT T CTC AAG AGC AAC CTC TTA GGG TTT ACG CCG CAT GTA AAA CAG TAT GGT GGG CGA A E F S L E N P K C G V H F V I P P A 550 560 570 580 590 * * * * * GAC GAG GAG ACA CAG ATG AAC AGC TCG CAT ATG TTC ACC AAT TGC TAT GAA AAC T CTG CTC CTC TGT GTC TAC TTG TCG AGC GTA TAC AAG TGG TTA ACG ATA CTT TTG A D E E T Q M N S S H M F T N C Y E N 610 620 630 640 650 149 PA \o AGA TTG TGG TTT CCC TGC GTG GAC AGT TTC GCC GAT CCC TGC ACC TGG CGG CTG GA TCT AAC ACC AAA GGG ACG CAC CTG TCA AAG CGG CTA GGG ACG TGG ACC GCC GAC CT R L W F P C V D S F A D P C T R L E 670 680 690 700 710 * * * * * ACT GTC GAC AAA AAT ATG ACC GCC GTT TCG TGT GGA GAA CTT CTA GAA GTC ATT AT TGA CAG CTG TTT TTA TAC TGG CGG CAA AGC ACA CCT CTT GAA GAT CTT CAG TAA TA T V D K N M T A V S C G E L L E V I M 730 740 750 760 770 * * * * * CCA GAT CTG CGA AAG AAA ACC TTC CAC TAT TCG GTT AGC ACA CCA GTA TGT GCA CC GGT CTA GAC GCT TTC TTT TGG AAG GTG ATA AGC CAA TCG TGT GGT CAT ACA CGT GG P D L R K K T F H Y S V S T P V C A P 790 800 810 820 830 * * * * * ATT GCG CTG GCT GTG GGT CAG TTT GAG ATC TAC GTG GAT CCG CAC ATG CAT GAA GT TAA CGC GAC CGA CAC CCA GTC AAA CTC TAG ATG CAC CTA GGC GTG TAC GTA CTT CA I A L A V G Q F E I Y V D P K M H E V 850 860 870 880 890 * * * * * CAC TTT TGT CTG CCC GGA TTG TTG CCG CTG TTA AAA AAT ACG GTT CGC TAT TTG CA GTG AAA ACA GAC GGG CCT AAC AAC GGC GAC AAT TTT TTA TGC CAA GCG ATA AAC GT H F C L P G L L P L L K N T V R Y L H 910 920 930 940 950 * * * * * GCA TTT GAA TTT TAC GAG GAG ACC TTA TCT ACG CGC TAC CCA TTC AGT TGC TAC AA CGT AAA CTT AAA ATG CTC CTC TGG AAT AGA TGC GCG ATG GGT AAG TCA ACG ATG TT A F E F Y E E T L S T R Y P F S C Y K 970 980 990 1000 1010 + * * * * GTG TTT GTA GAC GAA TTG GAC ACG GAC ATA AGT GCC TAT GCC ACT ATG AGC ATT GC CAC AAA CAT CTG CTT AAC CTG TGC CTG TAT TCA CGG ATA CGG TGA TAC TCG TAA CG V F V D E L D T D I S A Y A T M S I A 1030 1040 1050 1060 1070 * * * * * GTG AAC CTG CTG CAC TCC ATA GCT ATC ATC GAT CAG ACC TAT ATA TCT CGA ACC TT CAC TTG GAC GAC GTG AGG TAT CGA TAG TAG CTA GTC TGG ATA TAT AGA GCT TGG AA V N L L H S I A I I D Q T Y I S R T F 1090 1100 1110 1120 1130 * * * * * TCG CGC GCT GTG GCT GAG CAA TTC TTC GGC TGC TTT ATT ACA TCG CAT CAT TGG TC AGC GCG CGA CAC CGA CTC GTT AAG AAG CCG ACG AAA TAA TGT AGC GTA GTA ACC AG S R A V A E Q F F G C F I T S H H S 1150 1160 1170 1180 1190 * * * * * ACC TGG CTG GCC AAG GGC ATT GCG GAG TAC CTG TGT GGA TTG TAT TCC AGG AAG TG TGG ACC GAC CGG TTC CCG TAA CGC CTC ATG GAC ACA CCT AAC ATA AGG TCC TTC AC T W L A K G I A E Y L C G L Y S R K C 1210 1220 1230 1240 1250 ★ * * * * GGC AAC AAC GAG TAC CGT GCT TGG GTG CAA TCT GAA CTG GCG CGT GTC GTT CGC TA 150 CCG TTG TTG CTC ATG GCA CGA ACC CAC GTT AGA CTT GAC CGC GCA CAG CAA GCG AT G N N E Y R A W V Q S E L A R V V R Y 1270 1280 1290 1300 1310 ★ * * * * GAG CAG TAT GGC GGC ATT ATT CTC GAT TGC AGT CAG CCG CCA GCA CCT TTG CCT GT CTC GTC ATA CCG CCG TAA TAA GAG CTA ACG TCA GTC GGC GGT CGT GGA AAC GGA C E Q Y G G I I L D C S Q P P A P L P 1330 1340 1350 1360 1370 * GGC ACA AAT CAA TCG GCT GCT TCC AGC AAA CAG CAG GAG ATT GTC CAC TAT TTT C CCG TGT TTA GTT AGC CGA CGA AGG TCG TTT GTC GTC CTC TAA CAG GTG ATA AAA G G T N Q S A A S S K Q Q E I V H Y F P 1390 1400 1410 1420 1430 AAG AGT TTG CAC ACC GTA TCG CCG AAG TAT GTG GAG GCG ATG CGA AGG AAA GCG C TTC TCA AAC GTG TGG CAT AGC GGC TTC ATA CAC CTC CGC TAC GCT TCC TTT CGC G K S L H T V S P K Y V E A M R R K A 1450 1460 1470 1480 1490 * * * * * GTA ATC CGA ATG CTG GAG AAC CGC ATC GGG CAG GAG CTG CTG ATT CAG GTG TTC A CAT TAG GCT TAC GAC CTC TTG GCG TAG CCC GTC CTC GAC GAC TAA GTC CAC AAG T V I R M L E N R I G Q E L L I Q V F 1510 1520 1530 1540 1550 * CAA TTG GCT TTG GCT TCT AGT GCG GCA ACG ACG AAG ATC GGT GCA GGA CTC TGG T GTT AAC CGA AAC CGA AGA TCA CGC CGT TGC TGC TTC TAG CCA CGT CCT GAG ACC A Q L A L A S S A A T T K I G A G L W 1570 1580 1590 1600 1610 CTG CTC ATC TCG AAC CAA CAT TTT TAT CAA GGC CAT CTT CAC GTA ACC GGA AAA G GAC GAG TAG AGC TTG GTT GTA AAA ATA GTT CCG GTA GAA GTG CAT TGG CCT TTT C L L I S N Q H F Y Q G H L H V T G K ' 1630 1640 1650 1660 1670 TCT GTC TTC ATG GAC CAG TGG GTG CGC ACT GGA GGG CAC GCC AAG TTT TCG CTC A AGA CAG AAG TAC CTG GTC ACC CAC GCG TGA CCT CCC GTG CGG TTC AAA AGC GAG T S V F M D Q W V R T G G H A K F S L 1690 1700 1710 1720 1730 * * * * * GTG TTC AAT CGC AAG AGA AAC ACG ATT GAA CTG GAA ATC CGC CAG GAC TAT GTT A CAC AAG TTA GCG TTC TCT TTG TGC TAA CTT GAC CTT TAG GCG GTC CTG ATA CAA T V F N R K R N T I E L E I R Q D Y V 1750 1760 1770 1780 1790 * CGG GGA ATT AGA AAA TAC AAT GGT CCA TTG ATG GTG CAG CTG CAG GAG TTG GAT G GCC CCT TAA TCT TTT ATG TTA CCA GGT AAC TAC CAC GTC GAC GTC CTC AAC CTA C R G I R K Y N G P L M V Q L Q E L D 1810 1820 1830 1840 1850 TTT AAG CAC ACA TTG CAG ATT GAG AGT ACC CTG GTA AAG TCC GAT ATC ACT TGT C AAA TTC GTG TGT AAC GTC TAA CTC TCA TGG GAC CAT TTC AGG CTA TAG TGA ACA G F K H T L Q I E S T L V K S D I T C 151 1870 1880 1890 1900 1910 AAG AGC AGG CGT AAC AAA AAG AAG AAG ATC CCC TTG TGC ACC GGT GAG GAA GTG G TTC TCG TCC GCA TTG TTT TTC TTC TTC TAG GGG AAC ACG TGG CCA CTC CTT CAC C K S R R N K K K K I P L C T G E E V 1930 1940 1950 1960 1970 GAT TTA TCA GCC ATG GAC GAC TCA CCT GTG CTT TGG ATC CGC CTC GAT CCC GAA A CTA AAT AGT CGG TAC CTG CTG AGT GGA CAC GAA ACC TAG GCG GAG CTA GGG CTT T D L S A M D D S P V L W I R L D P E 1990 2000 2010 2020 2030 * CTG CTG CGC GAC CTC ATA ATC GAA CAG CCC GAC TTC CAG TGG CAG TAT CAG CTT C GAC GAC GCG CTG GAG TAT TAG CTT GTC GGG CTG AAG GTC ACC GTC ATA GTC GAA G L L R D L I I E Q P D F Q W Q Y Q L 2050 2060 2070 2080 2090 GAA CGT GAT GTT ACT GCT CAA TTT CAG GCG ATT CAA GCC CTG CAA AAG TAC CCC A CTT GCA CTA CAA TGA CGA GTT AAA GTC CGC TAA GTT CGG GAC GTT TTC ATG GGG T E R D V T A Q F Q A I Q A L Q K Y P 2110 2120 2130 2140 2150 GCC ACC AGG CTT GCT TTA ACC GAC ACC ATA GAA AGC GAA CGT TGC TTC TAT CAG G CGG TGG TCC GAA CGA AAT TGG CTG TGG TAT CTT TCG CTT GCA ACG AAG ATA GTC C A T R L A L T D T I E S E R C F Y Q 2170 2180 2190 2200 2210 * * * * * TGC GAG GCA GCC CAC AGC TTG ACC AAA GTG GCC AAC CAG ATG GTG GCC TCC TGG A ACG CTC CGT CGG GTG TCG AAC TGG TTT CAC CGG TTG GTC TAC CAC CGG AGG ACC T C E A A H S L T K V A N Q M V A S W 2230 2240 2250 2260 2270 * * * * * CCG CCC GCC ATG CTG AAC ATA TTT AGG AAG TTT TTC GGC TCA TTT AGT GCT CCG C GGC GGG CGG TAC GAC TTG TAT AAA TCC TTC AAA AAG CCG AGT AAA TCA CGA GGC G P P A M L N I F R K F F G S F S A P 2290 2300 2310 2320 2330 * * ATC AAA CTG AAC AAC TTC TCC AAC TTT CAG CTG TAC TTC CTG CAG AAG GCT ATT C TAG TTT GAC TTG TTG AAG AGG TTG AAA GTC GAC ATG AAG GAC GTC TTC CGA TAA G I K L N N F S N F Q L Y F L Q K A I 2350 2360 2370 2380 2390 * * * * * GCC ATG GCA GGT CTG CGC ACA TCT CAT GGT ATT TGC CCG CCG GAA GTG ATG CGT T CGG TAC CGT CCA GAC GCG TGT AGA GTA CCA TAA ACG GGC GGC CTT CAC TAC GCA A A M A G L R T S H G 1 C P P E V M R 2410 2420 2430 2440 2450 * * * * * TTC GAT CTC TTC AAG TAC AAC GAG AAT TCG CGT AAC CAT TAC ACG GAT GCA TAC T AAG CTA GAG AAG TTC ATG TTG CTC TTA AGC GCA TTG GTA ATG TGC CTA CGT ATG A F D L F K Y N E N S R N H Y T D A Y 2470 2480 2490 2500 2510 152 GCA GCT TTG GTA GAA GCT CTA GGC GAA ACC TTA ACA CCT GTG GTC TCC GTT GCT AT CGT CGA AAC CAT CTT CGA GAT CCG CTT TGG AAT TGT GGA CAC CAG AGG CAA CGA TA A A L V E A L G E T L T P V V S V A I 2530 2540 2550 2560 2570 * * * * * GGC ACA CAA ATC ACT ACG GAC AGT CTA TCC ACG GAT GCG AAA CTT GTG CTA GAT GA CCG TGT GTT TAG TGA TGC CTG TCA GAT AGG TGC CTA CGC TTT GAA CAC GAT CTA CT G T Q I T T D S L S T D A K L V L D E 2590 2600 2610 2620 2630 * * * * * ACA CGT CTG CTG AAC ATG GAG AAA CAT CTA CCC TCG TAC AAG TAC ATG GTG TCC GT TGT GCA GAC GAC TTG TAC CTC TTT GTA GAT GGG AGC ATG TTC ATG TAC CAC AGG CA T R L L N M E K H L P S Y K Y M V S V 2650 2660 2670 2680 2690 * * * * * TGT CTG AAG GTC ATC CGG AAG CTG CAA AAA TTC GGT CAT CTG CCC TCA CTG CCG CA ACA GAC TTC CAG TAG GCC TTC GAC GTT TTT AAG CCA GTA GAC GGG AGT GAC GGC GT C L K V I R K L Q K F G H L P S L P H 2710 2720 2730 2740 2750 * * * * * TAC CGC AGC TAT GCC GAA TAT GGA ATA TAT CTC GAT CTC CGC ATT GCT GCT ATG GA ATG GCG TCG ATA CGG CTT ATA CCT TAT ATA GAG CTA GAG GCG TAA CGA CGA TAC CT Y R S Y A E Y G I Y L D L R I A A M E 2770 2780 2790 2800 2810 * * * * * CTC GTG GAC TTT GTG AAA GTG GAT GGG CGC AGC GAG GAT TTG GAA CAT TTG ATT AC GAG CAC CTG AAA CAC TTT CAC CTA CCC GCG TCG CTC CTA AAC CTT GTA AAC TAA TG L V D F V K V D G R S E D L E H L I T 2830 2840 2850 2860 2870 * * * * * CTG GAA ACT GAT CCG GAT CCG GCT GCT CGC CAT GCA CTG GCC CAA CTG CTG ATC GA GAC CTT TGA CTA GGC CTA GGC CGA CGA GCG GTA CGT GAC CGG GTT GAC GAC TAG CT L E T D P D P A A R H A L A Q L L I D 2890 2900 2910 2920 2930 CCG CCT TTC ACA CGC GAA TCT CGC AGC CGT CTG GAT AAA CCC AAT CTC GTG GAT CG GGC GGA AAG TGT GCG CTT AGA GCG TCG GCA GAC CTA TTT GGG TTA GAG CAC CTA GC P P F T R E S R S R L D K P N L V D 2950 2960 2970 2980 2990 * * * * * TGG TTC AGT ATT AAT CGC TTG CCC TAC GAT ACC CAA STG CGC TGC GAT ATT GTC G ACC AAG TCA TAA TTA GCG AAC GGG ATG CTA TGG GTT SAC GCG ACG CTA TAA CAG C F S I N R L P Y D T Q X R C D I V D 3010 3020 3030 3040 3050 * * * * * TAC TAC GCA CTG TAC GGA ACT AAG CGT CCG AAT TGC TTG CAG GCC GGC GAG AAC C ATG ATG CGT GAC ATG CCT TGA TTC GCA GGC TTA ACG AAC GTC CGG CCG CTC TTG G Y Y A L Y G T K R P N C L Q A G E N 3070 3080 3090 3100 3110 * * * * * TTC TAC AAG GAT TTG ATG AAG GAC AAT AAT AGC AGT GTA GGC AGC GTA ACC GGC A 153 AAG ATG TTC CTA AAC TAC TTC CTG TTA TTA TCG TCA CAT CCG TCG CAT TGG CCG T F Y K D L M K D N N S S V G S V T G 3130 3140 3150 3160 3170 * * * * * AAG AAG ACC AGT GAT TCA AAG TCA CAT TTG CCA ACA CCA ACG AAT ACT TTG GAC A TTC TTC TGG TCA CTA AGT TTC AGT GTA AAC GGT TGT GGT TGC TTA TGA AAC CTG T K K T S D S K S H L P T P T N T L D 3190 3200 3210 3220 3230 * * * * * CCA CAG GAG CGG CAA AAG CCG GCA ATG GTT ACC ATC AAG CGA ACG GCC ACA GAA G GGT GTC CTC GCC GTT TTC GGC CGT TAC CAA TGG TAG TTC GCT TGC CGG TGT CTT C P Q E R Q K P A M V T I K R T A T E 3250 3260 3270 3280 3290 * * * * * GAG GTG GGC GAT GAG ATT ATC AAG CTG GAA CGC AGC GAG GAG ATC ACC GTG CTA G CTC CAC CCG CTA CTC TAA TAG TTC GAC CTT GCG TCG CTC CTC TAG TGG CAC GAT C E V G D E I I K L E R S E E I T V L 3310 3320 3330 3340 3350 * * * * * CCA GTT AAC GTG CAG GCC TAT GAC AGT GAG ACC AAA GTG AAT GCC CTG CAG GCA G GGT CAA TTG CAC GTC CGG ATA CTG TCA CTC TGG TTT CAC TTA CGG GAC GTC CGT C P V N V Q A Y D S E T K V N A L Q A 3370 3380 3390 3400 3410 * * * * * GAA GCA CGT GAT ACC CAT CAG GCT GCC AAG CGC CTT AAG AAC GAA ATG TAC GCC G CTT CGT GCA CTA TGG GTA GTC CGA CGG TTC GCG GAA TTC TTG CTT TAC ATG CGG C E A R D T H Q A A K R L K N E M Y A 3430 3440 3450 3460 3470 * * * * * GAT AAC TCA TCC ACA ATG CTC GAC GTG GGC GAC TCC ACC AGA TAT GAG AGT AGC C CTA TTG AGT AGG TGT TAC GAG CTG CAC CCG CTG AGG TGG TCT ATA CTC TCA TCG G D N S S T M L D V G D S T R Y E S S 3490 3500 3510 3520 3530 ★ * * * •* GAG GGC AAA TTG AAG TCC GGC GAT GGT GGG CTC AAG AAG AAA AAG AAG AAG GAG A CTC CCG TTT AAC TTC AGG CCG CTA CCA CCC GAG TTC TTC TTT TTC TTC TTC CTC T E G K L K S G D G G L K K K K K K E 3550 3560 3570 3580 3590 * * * * * AAG CAT AAG CAC AAA CVC AAG CAT AGG CAC AGC AAG GAC AAG GAC AAG GAG CGA A TTC GTA TTC GTG TTT GBG TTC GTA TCC GTG TCG TTC CTG TTC CTG TTC CTC GCT T K H K H K X K H R H S K D K D K E R 3610 3620 3630 3640 3650 * * * * * AAG GAC AAG CGT GAC CCG CAT ATA TTC ACC CTG CAG GCG CGC GAG ACA GCC ACT C TTC CTG TTC GCA CTG GGC GTA TAT AAG TGG GAC GTC CGC GCG CTC TGT CGG TGA G K D K R D P H I F T L Q A R E T A T 3670 3680 3690 3700 3710 * * * * * ACT CTC AGC TCG GAG GAC AGT AGC AAC AGC AAT AGC CTG CCG CCC ATG AAC CTT A TGA GAG TCG AGC CTC CTG TCA TCG TTG TCG TTA TCG GAC GGC GGG TAC TTG GAA T T L S S E D S S N S N S L P P M N L 154 3730 3740 3750 3760 3770 * * * * * GTG AGG GTT CCT ACA GGT GGG GAA ATT GCA ATG TTT GGG GGA TAG ATG ACA GAA TA CAC TCC CAA GGA TGT CCA CCC CTT TAA CGT TAC AAA CCC CCT ATC TAC TGT CTT AT V R V P T G G E I A M F G G ' M T E * 3790 3800 3810 3820 * * * * TAT AAT ACC TTA AAA AAA AAA AAA AAA AAA AAA AAA AAA A ATA TTA TGG AAT TTT TTT TTT TTT TTT TTT TTT TTT TTT T Y N T L K K K K K K K K K X> 155 LOCUS TRANSLDTAF 1217 A?. PROT FEATURES From To/Span Description Peptide 1 > 1217 67 to 3820 of dTAF150 (translated) [Split] < 1218 1218 67 to 3820 of dTAF150 (translated) [Split] 1 METQPEVPEV PLRPFKLAHQ WSLTGISFE RRSIIGWEL TIVPNSENLR LIRLNAKQLR 61 IYSWLNDVC QADFTYFDPF QNICYKEPKS RALEVYSKHH LTAAQYTDPD VNNGELLIQV 121 PPEGYSMIQE GQGLRIRIEF SLENPKCGVH FVIPPASTDE ETQMNSSHMF TNCYENSSRL 181 WFPCVDSFAD PCTWRLEFTV DKNMTAVSCG ELLEVIMTPD LRKKTFHYSV STPVCAPNIA 241 LAVGQFEIYV DPHMHEVTHF CLPGLLPLLK NTVRYLHEAF EFYEETLSTR YPFSCYKQVF 301 VDELDTDISA YATMSIASVN LLHSIAIIDQ TYISRTFMSR AVAEQFFGCF ITSHHWSDTW 361 LAKGIAEYLC GLYSRKCFGN NEYRAWVQSE LARWRYEEQ YGGIILDCSQ PPAPLPVSGT 421 NQSAASSKQQ EIVHYFPIKS LHTVSPKYVE AMRRKAHFVI RMLENRIGQE LLIQVFNKQL 481 ALASSAATTK IGAGLWSQLL ISNQHFYQGH LHVTGKDMSV FMDQWVRTGG HAKFSLTSVF 541 NRKRNTIELE IRQDYVNQRG IRKYNGPLMV QLQELDGTFK HTLQIESTLV KSDITCHSKS 601 RRNKKKKIPL CTGEEVDMDL SAMDDSPVLW IRLDPEMILL RDLIIEQPDF QWQYQLRHER 661 DVTAQFQAIQ ALQKYPTNAT RLALTDTIES ERCFYQVRCE AAHSLTKVAN QMVASWSGPP 721 AMLNIFRKFF GSFSAPHIIK LNNFSNFQLY FLQKAIPVAM AGLRTSHGIC PPEVMRFLFD 781 LFKYNENSRN HYTDAYYRAA LVEALGETLT PWSVAIHGT QITTDSLSTD AKLVLDEVTR 841 LLNMEKHLPS YKYMVSVSCL KVIRKLQKFG HLPSLPHIYR SYAEYGIYLD LRIAAMECLV 901 DFVKVDGRSE DLEHLITLLE TDPDPAARHA LAQLLIDNPP FTRESRSRLD KPNLVDRLWF 961 SINRLPYDTQ XRCDIVDLYY ALYGTKRPNC LQAGENQSFY KDLMKDNNSS VGSVTGSFKK 1021 TSDSKSHLPT PTNTLDNEPQ ERQKPAMVTI KRTATEAFEV GDEIIKLERS EEITVLDEPV 1081 NVQAYDSETK VNALQADEEA RDTHQAAKRL KNEMYAEDDN SSTMLDVGDS TRYESSHEEG 1141 KLKSGDGGLK KKKKKEKKKH KHKXKHRHSK DKDKERKDKD KRDPHIFTLQ ARETATPDTL 1201 SSEDSSNSNS LPPMNLN 1 5 6 Sequence Range: 1 to 872 10 20 30 40 50 60 * * * CCAAAAATCC GCCCAACTTA CTGTACTTTC CCCAAACACT TCCAACCAAC CGACCTACCA GGTTTTTAGG CGGGTTGAAT GACATGAAAG GGGTTTGTGA AGGTTGGTTG GCTGGATGGT 70 80 90 100 110 * * * * * CCCACTTGAT TTGACTCTGA AGAAACCCAA AAGCA ATG TCG GAT CTC TTT ACC ACT GGGTGAACTA AACTGAGACT TCTTTGGGTT TTCGT TAC AGC CTA GAG AAA TGG TGA M S D L F T T> TRANSLATION OF 802 F . 120 130 140 150 160 * * * * * TTC GAT AGC AAC GGC GTC GCG AGG CAC CAC CTG CAC CAC AAC CAC AAC AAG CTA TCG TTG CCG CAG CGC TCC GTG GTG GAC GTG GTG TTG GTG TTG F D S N G V A R H H L H H N H N> a TRANSLATION OF 802 FULL [A] > 170 180 190 200 210 * * * * * TCC ACA TCG TCC GCC AGC GGA CTG CTC CAC GAC CCA CCC ATG GCC TCG AGG TGT AGC AGG CGG TCG CCT GAC GAG GTG CTG GGT GGG TAC CGG AGC S T S S A S G L L H D P P M A S> a a a a TRANSLATION OF 802 FULL [A] a a a > 220 230 240 250 260 * CCC TCC CAG CAC AGT CCG ATG ACC AAC AAC AGC AAC TCA TCC TCG CAG GGG AGG GTC GTG TCA GGC TAC TGG TTG TTG TCG TTG AGT AGG AGC GTC P S Q H S P M T N N S N S S S Q> a a a a TRANSLATION OF 802 FULL [A] a a a a > 270 280 290 300 ★ * * * AAC GGC GGA CCG GTT TCC GGT TTG GGT ACG GGA ACG GGC CCC ATA TCT TTG CCG CCT GGC CAA AGG CCA AAC CCA TGC CCT TGC CCG GGG TAT AGA N G G P V S G L G T G T G P S> a a a a TRANSLATION OF 802 FULL [A] a a a 310 320 330 340 350 GGT GGT AGC AAG TCA TCC AAT CAC ACA TCA TCC GCC GCC GGT TCC GAG CCA CCA TCG TTC AGT AGG TTA GTG TGT AGT AGG CGG CGG CCA AGG CTC G G S K S S N H T S S A A G S E> a a a a TRANSLATION OF 802 FULL [A] a a a a > 360 370 380 390 400 * * * * * AAC ACT CCC ATG CTT ACC AAA CCG CGT CTC ACA GAG CTC GTC CGA GAG TTG TGA GGG TAC GAA TGG TTT GGC GCA GAG TGT CTC GAG CAG GCT CTC N T P M L T K P R L T E L V R E> a a a a TRANSLATION OF 802 FULL [A] a a a a > 410 420 430 440 450 GTG GAT ACC ACC ACG CAG CTG GAC GAG GAT GTT GAG GAG CTT CTG CTT CAC CTA TGG TGG TGC GTC GAC CTG CTC CTA CAA CTC CTC GAA GAC GAA V D T T T Q L D E D ) VV E E L L L> a TRANSLATION OF 802 FULL [A] > P(( ---> 157 sr & 460 470 480 490 500 CAG ATC ATC GAC GAC TTT GTG AGG GAC ACC GTC AAG TCG ACG AGC GCC GTC TAG TAG CTG CTG AAA CAC TCC CTG TGG CAG TTC AGC TGC TCG CGG Q I I D D F V R D T V K S T S A> a a a a TRANSLATION OF 802 FULL [A] a a a a > 510 520 530 540 * TTC GCC AAG CAC CGA AAG TCT AAC AAG ATC GAG GTG CGC GAC GTG CAG AAG CGG TTC GTG GCT TTC AGA TTG TTC TAG CTC CAC GCG CTG CAC GTC F A K H R K S N K I E V R D V Q> a a a a TRANSLATION OF 802 FULL [A] a a a a > 550 560 570 580 590 * * * * * CTG CAC TTT GAG CGG AAG TAC AAC ATG TGG ATA CCC GGC TTC GGT ACG GAC GTG AAA CTC GCC TTC ATG TTG TAC ACC TAT GGG CCG AAG CCA TGC L H F E R K Y N M I P G F G T> a a a a TRANSLATION OF 802 FULL [A] a a a a > 600 610 620 630 640 GAC GAA CTG CGT CCC TAC AAG CGG GCA GCT GTC ACG GAG GCG CAC AAA CTG CTT GAC GCA GGG ATG TTC GCC CGT CGA CAG TGC CTC CGC GTG TTT D E L R P Y K R A A V T E A H K> a a a a TRANSLATION OF 802 FULL [A] a a a a > 650 660 670 680 690 * * * * * CAG CGC CTT GCC CTC ATA CGG AAA ACG ATC AAG AAA TAC TAG AGGA GTC GCG GAA CGG GAG TAT GCC TTT TGC TAG TTC TTT ATG ATC TCCT Q R L A L I R K T I K K Y *> a a a TRANSLATION OF 802 FULL [A] a a a > AA TT 158 Sequence Range: 1 to 739 ( >&& ^ / fc ^Z-3 — 2-<-/J 10 20 30 40 50 * * * * * CCCCCCCCCC CCCCCCCCGA TTTTTTTTAA ATG GAC GAA ATC CTC TTT CCC ACG GGGGGGGGGG GGGGGGGGCT AAAAAAAATT TAC CTG CTT TAG GAG AAA GGG TGC M D E I L F P T> TRANSLATION OF 911G FULL > 60 70 80 90 100 * * * * * CAG CAA AAG AGC AAC TCC CTA AGC GAC GGC GAC GAT GTC GAC CTG AAA GTC GTT TTC TCG TTG AGG GAT TCG CTG CCG CTG CTA CAG CTG GAC TTT Q Q K S N S L S ® G (E> (D. V φ L K> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 110 120 130 140 150 * * * * * TTC TTC CAG TCG GGC CTC CGG GGG AGG CGA AAG GAC AGC GAC ACC TCG AAG AAG GTC AGC CCG GAG GCC CCC TCC GCT TTC CTG TCG CTG TGG AGC F F Q S G L R G R R K (D / S (D_ T S> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 160 170 180 190 * * * * GAT CCG GGA AAC GAT GCG GAT CGT GAT GGC AAA GAT GCG GAT GGG GAC CTA GGC CCT TTG CTA CGC CTA GCA CTA CCG TTT CTA CGC CTA CCC CTG D) P G N (jj) A ft R φ) G K D) A (B G (β a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 200 210 220 230 240 * * * * * AAC GAC AAC AAG AAC ACG GAC GGA GAT GGT GAC TCT GGC GAG CCG GCG TTG CTG TTG TTC TTG TGC CTG CCT CTA CCA CTG AGA CCG CTC GGC CGC N (J N K N T Q) G Cp> G £) S G (g> P A> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 250 260 270 280 290 * * • * * * CAC AAA AAG CTC AAA ACC AAG AAG GAA CTG GAG GAG GAG GAG CGC GAA GTG TTT TTC GAG TTT TGG TTC TTC CTT GAC CTC CTC CTC CTC GCG CTT H K K L K T K K E L E E E E R E> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 300 310 320 330 340 * * * * * CGA ATG CAG GTT CTC GTT TCC AAC TTT ACT GAA GAA CAG CTG GAT CGC GCT TAC GTC CAA GAG CAA AGG TTG AAA TGA CTT CTT GTC GAC CTA GCG R M Q V L V S N F T E E Q L D R a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 350 360 370 380 390 * * * * * TAC GAA ATG TAT CGT CGC TCA GCC TTT CCC AAG GCC GCC GTC AAG CGT ATG CTT TAC ATA GCA GCG AGT CGG AAA GGG TTC CGG CGG CAG TTC GCA Y E M Y R R S A F P K A A V K R> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 400 410 420 430 * * * * CTA ATG CAA ACT ATC ACC GGC TGT TCC GTG TCC CAA AAT GTT GTG ATA GAT TAC GTT TGA TAG TGG CCG ACA AGG CAC AGG GTT TTA CAA CAC TAT 159 b L M Q T I T G C S V S Q N V V I> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 440 450 460 470 480 ★ * * * ★ GCC ATG TCC GGC ATT GCG AAG GTC TTC GTC GGC GAG GTT GTG GAG GAA CGG TAC AGG CCG TAA CGC TTC CAG AAG CAG CCG CTC CAA CAC CTC CTT A M S G I A K V F V G E V V E E> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 490 500 510 520 530 * * * * * GCC CTC GAC GTG ATG GAG GCC CAA GGT GAA TCC GGT GCC CTG CAG CCC CGG GAG CTG CAC TAC CTC CGG GTT CCA CTT AGG CCA CGG GAC GTC GGG A L D V M E A Q G E S G A L Q P> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 540 550 560 570 580 * * * * * AAA TTC ATA CGA GAG GCA GTG CGA CGA CTG AGG ACC AAG GAT CGG ATG TTT AAG TAT GCT CTC CGT CAC GCT GCT GAC TCC TGG TTC CTA GCC TAC K F I R E A V R R L R T K D R M> a a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 590 600 610 620 630 * ★ ★ * * CCC ATA GGC AGA TAC CAG CAG CCC TAT TTC AGA CTG AAC TAG C GAGTC GGG TAT CCG TCT ATG GTC GTC GGG ATA AAG TCT GAC TTG ATC G CTCAG P I G R Y Q Q P Y F R L N * X> a a TRANSLATION OF 911G FULL 5/20 [A] a a a > 640 650 660 670 680 690 * * * * * * GAGACATTAA GAAATATAGT TTGTAAATCT GTTAGTGAAT ATAAAAATAC ATAAACAAGT CTCTGTAATT CTTTATATCA AACATTTAGA CAATCACTTA TATTTTTATG TATTTGTTCA 700 710 720 730 * * * * AAAAAGTAAA TAAATATAAA GATTTTTTCA AGAAAAAAAA AAAAAAAAG TTTTTCATTT ATTTATATTT CTAAAAAAGT TCTTTTTTTT TTTTTTTTC 160 10 20 30 40 * * ACC ATG TTG CTT CCG AAC ATC CTG CTC ACC GGT ACA CCA GGG GTT GGA TGG TAC AAC GAA GGC 'lTG TAG GAC GAG TGG CCA TGT GGT CCC CAA CCT 50 60 70 80 90 * _ _ _ AAA ACC ACA CTA GGC AAA GAA CTT GCG TCA AAA TCA GGA CTG AAA TAC TTT TGG TGT GAT CCG TTT CTT GAA CGC AGT TTT ΛGT CCT GAC TTT ATG 100 110 120 1.30 140 * ATT ΛAT CTG GGT GAT TTA GCT CGA GAA GTC TGA TCA TCG GAT ATC ATG TAA TTA CAC CCΛ CTA AAT CGA GCT CTT CAG ACT AGT AGC CTA TAG TAC M 150 160 170 180 190 * * GAG TCT GGC AAG ACG GCT TCT CCC AAG AGC ATG CCG AAA GAT GCA CAG CTC AGA CCG TTC TGC CGA AGA GGG TTC TCG TAC GGC TTT CTA CGT GTC K S G K T A S P K S M P K D A Q 200 210 230 240 * * ATG ATG GCA CAA ATC CTG AAG GAT ATG GGG ATT ACA GAA TAT GAG CCA TAC TAC CCT GTT TAG GAC TTC CTA TAC CCC TAA TGT C'l ATA CTC GGT -_ M A Q 1 L K D M G I T E Y E P> 250 260 270 280 _ AGA GTT ATA AAT CAG ATG TTG GAC TTT GCC TTC CGA TAT GTC ACC ACA TCT CAA TAT TTA GTC TAC AAC CTC AAA CGG AAG GCT ATA CAC TGG TGT R V Ϊ W Q M L E F A . , R Y V T> 90 300 310 320 330 _ * * ATT CTA GAT GAT GCA AAA ATT TAT TCA AGC CAT GCT ΛAC AAA GCT ACT TAA GAT CTA CTA CGT TTT TAA ΛTΛ ACT TCG GTA CGA TTC TTT CGA TCA I L D D A K Ϊ Y S S H Λ K K A > 340 350 360 370 380 * GTT GAT GCA GAT GAT GTG CGA TTG GCA ATC CAG TGC CGC GCT GAT CAG CAA CTA CGT CTA CTA CAC GCT AAC CGT TAG CTC ACG GCG CGA CTA GTC V D A D D V R L A I Q C R Λ D Q> 390 400 410 420 430 * * * TCT TTT ACC TCT CCT CCC CCA AGA GAT TTT TTA TTA GAT ATT GCA A G ΛGA AAA TGG AGA GGA GGG GGT TCT CTA AAA AAT AAT CTA TAA CGT TCC F T S P P P R D F I, L D I A R 440 450 460 470 480 * * * CAA AGA AAT CAA ACC CCT TTG CCA TTG ATC AAG CCA TAT TCA GGT CCT GTT TCT TTA GTT TGG GGA AAC GGT AAC TAG TTC GGT ATA AGT CCA GGA Q R N Q T P P L I K P Y S G P> 490 500 510 520 16 1 AGC TTG CCA CCT GAT AGA TAC TGC TTA ACA GCT CCA AAC TAT AGG CTG TCC AAC GGT GGA CTA TCT ATG ACG AAT TGT CGA GGT TTC ATA TCC GAC R L P P D R Y C J_ -' ' A P N R L> 530 540 550 560 5 0 * * AAA TCT TTA CAG AAA AAG GCA TCA ACT TCT GCG GGA AGA ATA ACA GTC TTT AGA AAT GTC TTT TTC CGT AGT TGA AGA CGC CCT TCT TAT TCT CAG K S L Q K K A S T Ξ A G R Ϊ T V 580 590 600 610 620 + * CCG CGG TTA AGT GTT GGT TCA GTT ACT AGC AGA CCA AGT ACT CCC ACA GGC GCC AAT TCA CAA CCA AGT CAA TGA TCG TCT GGT TCA TGA GGC. TGT P R L S V G S V T S R P S T P > 630 640 650 660 670 •* * * _ CTA GGC ACA CCA ACC CCA CAG ACC ATG TCT GTT TCA ACT AAA GTA GGG GAT CCG TGT GGT TGG GGT GTC TGG TAC AGA CAA AGT TGA TTT CAT CCC r, G T P T P 0 T M S V S T K V G> 680 690 700 710 720 * * ACT CCC ATC TCC CTC ACA GGT CAA AGC TTT ACA GTA CAG ATG CCT ACT TGA GGG TAC AGG GAG TGT CCA GTT TCC AAA TGT CAT GTC TAC GGA TGA T P K S L T G Q R F T V Q M P T 730 740 750 760 * * * * TCT CAG TCT CCA GCT GTΛ ΛΛλ GCT TCA ATT CCT GCA ACC TCA GCA GTT AGA GTC AGA GGT CGA CAT TTT CGA AGT TAA GGA CGT TGG AGT CGT CAA £ Q S P A V K A S I P A T S A > 770 780 790 800 810 + * * CAG AAT GTT CTG ATT AAT CCA TCA TTA ATC GGG TCC AAA AAC ATT CTT GTC TTA CAA GAC TAA TTA GGT AGT AAT TAG CCC AGG TTT TTG TΛΛ GΛΛ Q N V L I N P S L I G S K N I > 820 830 840 850 860 * ATT ACC ACT AAT ATG ATG TCA TCA CAA AAT ACT GCC AAT GAA TCA TCA TAA TGG TGA TTA TAC TAC AGT AGT GTT TTA TGA CGG TTA CTT AGT AGT I T T N M M S S Q N T Λ N E S S> 870 880 890 900 910 * * AAT GCA TTG AAA AGA AAA CGT GAA GAT GAT GAT GAT GAC GAT GAT GAT "TTA CGT AAC TTT TCT TTT GCA CTT CTA CTA CTA CTA CTG CTA CTA CTΛ N A L K R K R E D D D D D D D D> 920 930 940 950 960 * * GAT GAT GAC TAT GAT AAT CTG TAA TCT AGC CTT GCT GAA TGT AAC ATG CTA CTA CTG ATA CTA TTA GAC ATT AGA TCG GAA CGA CTT ACA TTG TAC D D D Y D N L> 970 980 990 1000 * * TAT ACT TGG TCT TGA ATT CAT TGT ACT GAT ATT AAA CAT GCA TGC TGG ATA TGA ACC AGA ACT TAA GTA ACA TGA CTA TAA TTT GTA CGT ACG ACC 162 10 1020 1030 1040 1050 * * * * * A'i._ TTT TCA AGT TGT GTT TTA GΛΛ AAC TAA TAA TAA TGA GTA AAC ACA TAC AAA AGT TCA ACA CAA AAT C'lT TTC. ATT ATT ATT ACT CAT TTG TGT 1060 1070 1080 1090 1100 _ _ * * * GTT ACC ATA CTT TTC AAT TGA AAT GAA GGT TTT TCA TCA GCC TTA AAA CAA TGG TAT GAA AAG TTA ACT TTA CTT CCA ΛΛΛ ΛGT ACT CGG AAT TTT 1110 1120 1.130 1140 1150 * * * _ * GTG TAA GAA AAA TAA AGT TGT CAT TCA -'It: GAT AAA AAA AAA AAA A CAC ATT CTT TTT ATT TCA ACA GTA AGT AAG CTA TTT TTT TTT TTT T 1 6 3 hTAFIBOα peptides: <£? & Λ£ 9-1 " ) 1. DVQ HLERQ_NMJPGFGSEEI_PYK 2. KKLQDLVREVDPNEQLDEDV_EML QIADD 3. LQDLVREVDPN TAFII30β peptides: ≤ / _ <_ $ | £> 1. VFVGEWEEALDVEEKP 2. HMREAVRRLX 3. MQILVSSFEEEQLN_YE YN_K_AYGQ 164 hTAF I 48 -> Genes DNA sequence 1578 b.p. ATTCCAAGCTAA ... GTCTGTTTTCTT linear Read from Bionet/Intelligenetics file ".8 prot" 1 ATTCCAAGCTAAATTTAGGCGGGT ATG AGT GAT TTC AGT GAA GAA TTA AAA GGG CCT GTG ACA GAT 66 1 M S D F S E E L K G P V T D 14 67 GAT GAA GAA GTG GAA ACA TCT GTG CTC AGT GGT GCA GGA ATG CAT TTT CCT TGG CTT CAA 126 15 D E E V E T S V L S G A G M H F P L Q 34 127 ACA TAC GTA GAA ACT GTG GCC ATT GGA GGG AAA AGG AGG AAG GAT TTT GCT CAG ACA ACA 186 35 T Y V E T V A I G G K R R K D F A Q T T 54 187 AGT GCT TGT TTA AGT TTT ATC CAA GAA GCT CTG CTG AAG CAC CAA TGG CAG CAA GCT GCA 246 55 S A C L S F I Q E A L K H Q Q Q A A 74 247 GAA TAC ATG TAC AGT TAT TTT CAG ACC TTG GAA GAT TCA GAT AGC TAC AAA AGG CAG GCT 306 75 E Y -1 Y S Y F Q T L E D S D S Y K R Q A 94 307 GCA CCT GAG ATT ATT TGG AAG CTC GGA AGT GAA ATT CTA TTT TAT CAT CCC AAA AGC AAC 366 95 A P E I I W K L G S E I L F Y H P K S N 114 367 ATG GAG AGT TTC AAT ACT TTT GCT AAC CGG ATG AAA AAT ATT GGC GTC ATG AAT TAT TTA 426 115 M E S F N T F A N R M K N 1 G V M N 134 427 AAG ATC TCC TTA CAA CAT GCA TTA TAC CTT CTG CAT CAT GGA ATG CTT AAA GAT GCT AAG 486 135 K I S L Q H A Y H H G M L K D A K 154 487 AGA AAT CTG AGT GAG GCA GAG ACA TGG AGA CAT GGT GAA AAT ACG TCT TCC CGG GAA ATA 546 155 R N L S E A E T W R H G E N T S S R E I 174 547 TTA ATC AAC CTT ATT CAG GCC TAT AAA GGG CTT TTA CAG TAT TAT ACC TGG TCT GAA AAG 606 175 L I N L I Q A Y K G L L Q Y Y T W S E K 194 607 AAG ATG GAA TTG TCA AAG CTT GAT AAG GAT GAT TAT GCT TAC AAT GCA GTA GCC CAG GAT 666 195 K M E L S K L D K D D Y A Y N A V A Q D 214 667 GTG TTC AAC CAC AGC TGG AAG ACA TCT GCA AAT ATT TCT GCA TTG ATT AAA ATT CCT GGA 726 215 V F N H S W K T S A N I S A L I K I P G 234 727 GTT TGG GAC CCT TTT GTG AAG AGT TAT GTA GAA ATG CTG GAA TTC TAT GGG GAT CGA GAT 786 235 V W D P F V K S Y V E M L E F Y G D R D 254 787 GGA GCC CAA GAG GTA CTC ACC AAT TAT GCA TAT GAT GAA AAG TTT CCA TCA AAT CCA AAT 846 255 G A Q E V T N Y A Y D E K F P S N P N 274 847 GCC CAT ATC TAC TTA TAC AAC TTT CTA AAG AGA CAG AAG GCA CCA AGA TCA AAA TTG ATA 906 275 A H I Y L Y N F K R Q K A P R S K L I 294 907 AGT GTG CTT AAG ATT TTG TAT CAG ATT GTA CCA TCT CAT AAA TTG ATG TTG GAA TTC CAT 966 295 S V L K I L Y Q I V P S H K L M L E F H 314 967 ACA TTA CTT AGA AAA TCA GAA AAA GAA GAA CAC CGT AAA CTG GGG TTG GAG GTA TTA TTT 1026 315 T L R K S E K E E H R K L G L E V L F 334 1027 GGA GTC TTA GAT TTT GCC GGA TGC ACT AAG AAT ATA ACT GCT TGG AAA TAC TTG GCA AAA 1086 335 G V L D F A G C T K N I T A W K Y L A K 354 1087 TAT CTG AAA AAT ATC TTA ATG GGA AAC CAC CTT GCG TGG GTT CAA GAA GAG TGG AAC TCC 1146 355 Y L K N I L M G N H A W V Q E E W S 374 1147 AGG AAA AAC TGG TGG CCA GGG TTT CAT TTC AGC TAC TTT TGG GCA AAA AGT GAT TGG AAG 1206 375 R K N W W P G F H F S Y F W A K S D W K 394 1207 GAA GAT ACA GCT TTG GCC TGT GAG AAA GCT TTT GTG GCT GGT TTA CTG TTA GGA AAA GGT 1266 395 E D T A L A C E K A F V A G L G K G 414 1267 TGT AGA TAT TTC CGG TAT ATT TTA AAG CAA GAT CAC CAA ATC TTA GGG AAG AAA ATT AAG 1326 415 C R Y F R Y Ϊ - K Q D H Q I L G K K I K 434 1327 CGG ATG AAG AGA TCT GTG AAA AAA TAC AGT ATT GTA AAT CCA AGA CTC TGA TACTGAATTTTA 1389 435 R X K R S V K K Y S I N P L - 451 165 pie. ( / hTAFillO cDNA and deduced a ino acid sequence Dr. R. Tjian laboratory, Department of Molecular and Cell Biology, University of California, Berkeley. 10 20 30 40 50 * * * * * GCTCGAGTGCCAAAGCTGGGGTTCTACTTGAGATTTCCCTCGTGGTGCCA 60 70 80 90 100 * * * * * GGGTCCGGCGAGCATCACGCCGAGGCCCATTTTCCAGACGACCACGACGA 110 120 130 140 150 * * * * * GGCCGGGGTCACGAACTCTGGCGCCCCTTACCAGCTTCCAGTCTCTCGAG 160 170 180 190 200 * * * * * GTGGCCAGTGTGGTGCTTGGTCCTTGTTTCCAGGATGGACTTCCCCAGCT M D F P S> 210 220 230 240 250 * * * * * CCCTCCGCCCTGCGTTGTTTCTGACCGGCCCCCTTGGTCTGAGCGACGTC S L R P A L F L T G P L G L S D V> 260 270 280 290 300 * * * * * CCTGACCTCTCTTTCATGTGCAGCTGGCGAGACGCACTGACTCTGCCAGA P D L S F M C S W R D A L T L P E> 310 320 330 340 350 * * * * * GGCCCAGCCCCAGAACTCAGAGAATGGGGCACTGCATGTGACCAAGGACC A Q P Q N S E N G A L H V T K D> 360 370 380 390 400 * * * * * TGCTGTGGGAGCCGGCAACCCCTGGGCCTCTCCCCATGCTGCCTCCCCTC L L W E P A T P G P L P M L P P > 410 420 430 440 450 * * * * * ATCGATCCCTGGGACCCTGGCCTGACTGCCCGGGACCTGCTTTTCCGCGG I D P W D P G L T A R D L L F R O 460 470 480 490 500 * * * * * AGGGTACCGGTATCGGAAGCGGCCCCGAGTCGTGCTGGATGTGACTGAGC G Y R Y R K R P R V V L D V T E> 166 pi. fZ- 510 520 530 540 550 * * * * * AGATCAGCCGGTTCCTCTTGGATCATGGAGACGTAGCCTTTGCGCCCCTG Q I S R F L L D H G D V A F A P > 560 570 580 590 600 * * * * * GGGAAGCTGATGCTGGAGAATTTCAAGCTGGAGGGAGCGGGGAGCCGCAC G K L M L E N F K L E G A G S R T> 610 620 630 640 650 * * * * * TAAGAAGAAGACAGTGGTCAGTGTGAAGAAGCTGCTCCAGGACCTCGGTG K K K T V V S V K K L L Q D O 660 670 680 690 700 * * * * * GACACCAGCCCTGGGGGTGTCCCTGGGCTTACCTCAGCAACCGACAGCGC G H Q P W G C P W A Y L S N R Q > 710 720 730 740 750 * * * * * CGCTTCTCTATCCTCGGGGGCCCCATCCTGGGCACGTCGGTGGCGAGCCA R F S I L G G P I L G T S V A S H> 760 770 780 790 800 * * * * * CTTGGCAGAGCTGCTGCACGAGGAGCTGGTGCTGCGGTGGGAGCAGCTGC L A E L L H E E L V L R W E Q L> 810 820 830 840 850 * * * * * TTCTGGATGAGGCCTGCACTGGGGGCGCGCTGGCCTGGGTTCCTGGAAGG L L D E A C T G G A L A W V P G R> 860 870 880 890 900 * * * * * ACACCCCAGTTCGGGCAGCTGGTCTACCCTGCTGGAGGCGCCCAGGACAG T P Q F G Q L V Y P A G G A Q D R> 910 920 930 940 950 * * * * * GCTGCATTTCCAAGAGGTCGTTCTGACCCCAGGTGACAATCCCCAATTCC L H F Q E V V L T P G D N P Q F> 960 970 980 990 1000 * * * * * TTGGGAAACCTGGACGCATCCAGCTCCAGGGACCTGTCCGGCAAGTGGTG L G K P G R I Q L Q G P V R Q V > 1010 1020 1030 1040 1050 * * * * * ACATGCACCGTCCAGGGAGAAAGTAAGGCCCTTATATACACTTTCCTCCC T C T V Q G E S K A L I Y T F L P> 167 1060 1070 1080 1090 1100 * * * * * TCACTGGCTGACCTGCTACCTGACCCCTGGCCCTTTCCATCCCTCCTCAG H W L T C Y L T P G P F H P S S> 1110 1120 1130 1140 1150 * * * * * CTCTGCTGGCCGTCCGCTCTGACTACCACTGTGCCGTGTGGAAGTTTGGT A L L A V R S D Y H C A V W K O 1160 1170 1180 1190 1200 * * * * * AAACAGTGGCAGCCAACCCTTCTGCAGGCGATGCAGGTGGAGAAAGGGGC K Q W Q P T L L Q A M Q V E K G A> 1210 1220 1230 1240 1250 * * * * * CACGGGGATCAGCCTCAGCCCTCACCTGCCCGGGGAGCTGGCCATCTGCA T G I S L S P H L P G E L A I O 1260 1270 1280 1290 1300 * * * * * GCCGCTCGGGAGCCGTCTGCCTGTGGAGCCCTGAGGATGGGCTGCGGCAA S R S G A V C L W S P E D G L Q> 1310 1320 1330 1340 1350 * * * * * ATCTACAGGGACCCTGAGACCCTCGTGTTCCGGGACTCCTCTTCGTGGCG I Y R D P E T L V F R D S S S W R> 1360 1370 1380 1390 1400 * * * * * TTGGGCAGACTTCACTGCGCACCCTCGGGTGCTGACCGTGGGTGACCGCA W A D F T A H P R V L T V G D > 1410 1420 1430 1440 1450 * * * * * CCGGAGTGAAGATGCTGGACACTCAGGGCCCGCCGGGCTGTGGTCTGTTG T G V K M L D T Q G P P G C G L L> 1460 1470 1480 1490 1500 * * * * * CTTTTTCGTTTGGGGGCAGAGGCTTCGTGCCAGAAAGGGGAACGTGTCCT L F R L G A E A S C Q K G E R V L> 1510 1520 1530 1540 1550 * * * * * GCTTACCCAGTACCTGGGGCACTCCAGCCCCAAATGCCTCCCCCCTACTC L T Q Y L G H S S P K C L P P T> 1560 1570 1580 1590 1600 * * * * * TTCATCTCGTCTGTACCCAGTTCTCTCTCTACCTAGTGGACGAGCGCCTT L H L V C T Q F S L Y L V D E R L> 168 1610 1620 1630 1640 1650 * * * * * CCCCTGGTGCCGATGCTGAAGTGGAACCATGGCCTCCCCTCCCCGCTCCT P L V P M L K W N H G L P S P L L> 1660 1670 1680 1690 1700 * * * * * GCTGGCCCGACTGCTGCCTCCGCCCCGGCCCAGCTGCGTGCAGCCCCTGC L A R L L P P P R P S C V Q P > 1710 1720 1730 1740 1750 * * * * * TCCTCGGAGGCCAGGGTGGGCAGCTGCAGCTGCTGCACCTGGCAGGAGAA L L G G Q G G Q L Q L L H L A G E> 1760 1770 1780 1790 1800 * * * * * GGGGCGTCGGTGCCCCGCCTGGCAGGCCCCCCCCAGTCTCTTCCTTCCAG G A S V P R L A G P P Q S L P S > 1810 1820 1830 1840 1850 * * * * * GATCGACTCCCTCCCTGCATTTCCTCTGCTGGAGCCTAAGATCCAGTGGC I D S L P A F P L L E P K I Q W> 1860 1870 1880 1890 1900 * * * * * GGCTGCAGGAGCGCCTGAAAGCACCGACCATAGGTCTGGCTGCCGTCGTC R L Q E R L K A P T I G L A A V V> 1910 1920 1930 1940 1950 * * * * * CCGCCCTTGCCCTCAGCGCCCACACCAGGCCTGGTGCTCTTCCAGCTCTC P P L P S A P T P G L V L F Q S> 1960 1970 1980 1990 2000 * * * * * GGCGGCGGGAGATGTCTTCTACCAGCAGCTCCGCCCCCAGGTGGACTCCA A A G D V F Y Q Q L R P Q V D S> 2010 2020 2030 2040 2050 * * * * * GCCTCCGCAGAGATGCTGGGCCTCCTGGCGACACCCAACCTGACTGCCAT S L R R D A G P P G D T Q P D C H> 2060 2070 2080 2090 2100 * * * * * GCCCCCACAGCTTCCTGGACCTCCCAGGACACTGCCGGCTGCAGCCAGTG A P T A S W T S Q D T A G C S Q W> 2110 2120 2130 2140 2150 * * * * * GCTGAAGGCCCTGCTAAAAGTGCCCCTGGCTCCTCCTGTGTGGACAGCAC L K A L L K V P L A P P V W T A> 169 2160 2170 2180 2190 2200 * * * * * CCACCTTCACCCACCGCCAGATGCTGGGCAGCACAGAGCTGCGGAGGGAG P T F T H R Q M L G S T E L R R E> 2210 2220 2230 2240 2250 * * * * * GAAGAGGAAGGGCAGCGGCTGGGTGTGCTCCGCAAGGCCATGGCCCGAGG E E E G Q R L G V L R K A M A R O 2260 2270 2280 2290 2300 * * * * * GCAGCTCCTGCTGCAGAGAGACCTGGGCTCCCTCCCTGCGGCAGAGCCAC Q L L L Q R D L G S L P A A E P> 2310 2320 2330 2340 2350 * * * * * CCCCTGCACCCGAGTCAGGCCTAGAGGACAAGCTCAGTGAGCGCCTGGGG P P A P E S G L E D K L S E R G> 2360 2370 2380 2390 2400 * * * * * GAAGCCTGGGCAGGCCGAGGGGCTGCCTGGTGGGAGAGGCAGCAGGGCAG E A W A G R G A A W W E R Q Q G > 2410 2420 2430 2440 2450 * * * * * GACCTCGGAGCCCGGGAGACAGACCAGGCGGCCCAAGCGCCGGACCCAGC T S E P G R Q T R R P K R R T Q> 2460 2470 2480 2490 2500 * * * * * TGTCCAGCAGCTTTTCGCTCAGTGGCCATGTGGATCCGTCAGAGGACACC L S S S F S L S G H V D P S E D T> 2510 2520 2530 2540 2550 * * * * * AGCTCCCCTCATAGCCCTGAGTGGCCACCTGCTGATGCTCTGCCCCTGCC S S P H S P E W P P A D A L P P> 2560 2570 2580 2590 2600 * * * * * CCCCACGACCCCGCCCTCCCAGGAGTTGACTCCGGATGCATGCGCCCAGG P T T P P S Q E L T P D A C A Q> 2610 2620 2630 2640 2650 * * * * * GCGTCCCATCAGAGCAGCGGCAGATGCTCCGTGACTACATGGCCAAGCTA G V P S E Q R Q M L R D Y M A K > 2660 2670 2680 2690 2700 * * * * * CCACCCCAGAGGGACACCCCAGGCTGTGCCACCACACCTCCCCACTCCCA P P Q R D T P G C A T T P P H S Q> 170 2710 2720 2730 2740 2750 * * * * * GGCCTCCAGCGTCCGGGCCACTCGCTCCCAGCAGCACACACCCGTCCTCT A S S V R A T R S Q Q H T P V > 2760 2770 2780 2790 2800 * * * * * CTAGCTCTCAGCCCCTCCGGAAGAAGCCTCGAATGGGCTTCTGAGGACAC S S S Q P L R K K P R M G F> 2810 2820 2830 2840 2850 * * * * * AAGGTGGGCTGCCCTCAAGCCCCAGAGAGCCCCTCATCCTTCCTCTGGGA 2860 2870 2880 2890 2900 * * * * * CCAGATGTGCCTTCCACAGTTGAAACTTGAGAAGCAGAGCTCGCCACCTT 2910 2920 2930 2940 2950 * * * * * CTGGAGGCCACTGTGATGATGAGCCAAGCAATTTGGAGCCAAGTTGAAGG 2960 2970 2980 2990 3000 * * * * * GACAGGGCAACAAAATACAGTAGTAGTTTCTTTTGTATTTTGTATATTCG 3010 3020 3030 3040 3050 * * * * * CCTGAAGATCATCCCGCAAGGCAGGCTGGAGGTGCCGGTGGGCCTGTGTT 3060 3070 3080 3090 3100 * * * * * GCTGGGATTTTAGTCTGTGCTGGGAGGCAGGGCTCCGTGCGCCTCAGCTG 3110 3120 3130 3140 3150 * * * * * TGGGGGCCTCAGGCAGGTCCCTCAGTTCTCACGCCTTCCTGTCCAGTGGA 3160 3170 3180 3190 3200 * * * * * ATGGGGGCCAGGAGTGCTGGCTCCTCGTGTTTGGTGAGGGTGGAGTGAGG 3210 3220 3230 3240 3250 * * * * * CCCCTGCAGAGCTGCTGATGAGGTGGGCACAGCGGCCGTTGGCAGCTGCT 3260 3270 3280 3290 3300 * * * * * GTTGTGGGTTGCTTTGTCAATCTCTGCCCCGGTCTGATGTTTCCTACAGG 3310 3320 3330 3340 3350 * * * * * GAGATGCCGTGGATCCAGGTTCAGGGACTAAATACACTTGGCAGCTGAAG 171 3360 3370 3380 3390 3400 * * * * * ATGAATTGGAATGGTCACGTTTTTTAGGCTGGNACAGCGTCCCGCCACAG 3410 3420 3430 3440 3450 * * * * * CTACTACCTGACACTGAGCTCATGCAGAGAGATGATGGCTGATGTTCCTT 3460 3470 3480 3490 3500 * * * * * CTCCCTTGGGACATGGGTCTGGCACCTGTGGGCTGTCGATAGTGCCCTCT 3510 3520 3530 3540 3550 * * * * * GAGCAGAGGGTCACGGTCATGTCAGTTTGGGGGAATTCTCTGTTGTGCCT 3560 3570 3580 3590 3600 * * * * * CAGAGACTCCCCCCTTTCTTTCCTCCCTCCCCTTCTCATTTTGATGTCTA 3610 3620 3630 3640 3650 * * * * * AAGCATCAAGTCCCTCTTCCTCAGAGTTTCTCTAGCTGCAGTGGAAGATT 3660 3670 3680 3690 3700 * * * * * CTGTTTTCCTGTGGGGAAAATGCTCACTTGAGATTTTGCAGGGACCCGGG 3710 3720 3730 3740 3750 * * * * * TCTGTCTGGTTTCTGATGACATAGTAAGAGAAAGGTCTTTTTTCAGGTTG 3760 3770 3780 3790 3800 * * * * * GCTGGTGAAAGGAATTGCATGTGACTCACACAAACAGGAGCTAGCCCAAT 3810 3820 3830 3840 3850 * * * * * CATACACTGACTCGCGTGGGTGTTTAAATGTTTATCATGCCTAAGGGAGA 3860 3870 3880 3890 3900 * * * * * CATTTATAATTAAACCATTTATGCTACATAAAAAAAAAAAAAAAAAAAAA AA 172 3360 3370 3380 3390 3400 * * * * * ATGAATTGGAATGGTCACGTTTTTTAGGCTGGNACAGCGTCCCGCCACAG 3410 3420 3430 3440 3450 * * * * * CTACTACCTGACACTGAGCTCATGCAGAGAGATGATGGCTGATGTTCCTT 3460 3470 3480 3490 3500 * * * * * CTCCCTTGGGACATGGGTCTGGCACCTGTGGGCTGTCGATAGTGCCCTCT 3510 3520 3530 3540 3550 * * * * * GAGCAGAGGGTCACGGTCATGTCAGTTTGGGGGAATTCTCTGTTGTGCCT 3560 3570 3580 3590 3600 * * * * * CAGAGACTCCCCCCTTTCTTTCCTCCCTCCCCTTCTCATTTTGATGTCTA 3610 3620 3630 3640 3650 * * * * * AAGCATCAAGTCCCTCTTCCTCAGAGTTTCTCTAGCTGCAGTGGAAGATT 3660 3670 3680 3690 3700 * * * * * CTGTTTTCCTGTGGGGAAAATGCTCACTTGAGATTTTGCAGGGACCCGGG 3710 3720 3730 3740 3750 * * * * * TCTGTCTGGTTTCTGATGACATAGTAAGAGAAAGGTCTTTTTTCAGGTTG 3760 3770 3780 3790 3800 * * * * * GCTGGTGAAAGGAATTGCATGTGACTCACACAAACAGGAGCTAGCCCAAT 3810 3820 3830 3840 3850 * * * * * CATACACTGACTCGCGTGGGTGTTTAAATGTTTATCATGCCTAAGGGAGA 3860 3870 3880 3890 3900 * * * * * CATTTATAATTAAACCATTTATGCTACATAAAAAAAAAAAAAAAAAAAAA AA 173

Claims: WHAT IS CLAIM 1.1) IS: 1. A composition comprising a substantially pure, biologically active portion of a TAF, wherein said TΛF is other than CCG 1. 2. A composition according to claim 1 wherein said portion is a substantially full-length TAF. 3. A composition according to claim 1 wherein said TAF is selected from the group consisting of dTAF250. dTΛFIUSO, dTAFIIl 10, dTAFII80, dTAFIIβO, dTAFII40 and dTAFII30. 4. A composition according to claim 1 wherein said TAF is selected from the group consisting of hTΛFH25(). I.TΛFII 150, hTAF-1130, hTAFIIlOO, hTAFII70, hTAFII40 and I.TAFII30. 5. A composition according to claim 1 wherein said TAF is selected from the group consisting of hTAFI l 10. I.TΛFI63 and hTAFI48. 6. A composition according to claim 1 wherein said TAF is selected from the group consisting of hTΛFI!I I72. and I.TAFIII25. 7. A composition comprising an isolated nucleic acid sequence encoding a portion of a TAF according to claim 1. 8. A composition according to claim 7 wherein said portion is a substantially full-length TAF. 9. A composition according to claim 7 wherein said TAF is selected from the group consisting o dTΛF250. dTΛlTI 150, dTAFII l 10, dTAFII80, dTAFIIβO, dTAFII40 and dTAFII30. 1 7 4 10. A composition according to claim 7 wherein said TAF is selected from the group consisting of " I.TΛFII250. I.TΛFII 150. 1VTAFII 130, hTAFIIlOO, hTAFII70, hTAFIMO and hTΛFII30. 11. A composition according to claim 7 wherein said TAF is selected from the group consisting of liTΛFM 10, hTAFI63 and hTAFI48. 12. A composition according to claim 7 wherein said TAF is selected from the group consisting of I.TAFIII I72, and hTAFIII25. 13. An antibody that specifically binds a composition according to Claim 1. 14. A vector comprising a nucleic acid sequence according to claim 7 operably linked to a transcription regulatory element. 15. A cell comprising a nucleic acid sequence according to claim 7. 16. A process for the production of a TAF comprising culturing the cell of Claim 15 under conditions suitable for the expression of said TAF and recovering said TAF. 17. A composition comprising a recombinantly produced TAF. 18. A method of identifying an agent useful in the diagnosis or treatment of disease associated with transcription, said method comprising the steps of: contacting an agent with at least a portion of a TAF according to claim 1; and, determining whether said agent specifically binds said TAF. 19. A method of identifying an agent useful in the diagnosis or treatment of disease associated with tran.scription. said method comprising the steps of: adding an agent to a mixture comprising at least a portion of a TAF according to claim I : 1 7 5 comparing the as.sociation of mixture components before and after said adding step; identifying an agent that alters the association of mixture components. 20. A method for treating disease, said method comprising: identifying an agent according to the method of claim 18; and, contacting an individual with said agent; wherein said agent modulates transcription in said individual. 21. A method for treating disease, said method comprising: identifying an agent according to the method of claim 19; and, contacting an individual with said agent; wherein said agent modulates transcription in said individual. 1 7 6

Inventors: COMAI LUCIO, DYNLACT BRIAN DAVID, HOEY TIMOTHY, RUPPERT SIEGFRIED, TANESE NAOKO, TJIAN ROBERT, WANG EDITH, WEINZIERL ROBERT O J, COMAI, LUCIO, DYNLACT, BRIAN, DAVID, HOEY, TIMOTHY, RUPPERT, SIEGFRIED, TANESE, NAOKO, TJIAN, ROBERT, WANG, EDITH, WEINZIERL, ROBERT, O., J.
Applicants: UNIV CALIFORNIA, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Application year: 1994
Main classification: C07H17
IPC codes: A61K38, A61K39, A61K45, C07K14, C07K16, C12N5, C12N15, C12P21, C12R1, G01N33